Compositions

ABSTRACT

The invention provides a colon cleansing solution comprising:
     a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of:
       (i) ascorbic acid and   (ii) one or more salts of ascorbic acid   the components (i) and (ii) being present in a molar ratio of from 1:4.5 to 1:7.0; and   
       b) 10 to 200 g per litre polyethylene glycol.   

     The invention also provides methods and kits associated with, or making use of the solutions, and compositions for the preparation of the solutions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/657,495, filed Mar. 13, 2015, in issue, which application is acontinuation of U.S. application Ser. No. 14/223,127, filed Mar. 24,2014, which application issued as U.S. Pat. No. 8,999,313 on Apr. 7,2015, which application is a continuation of international (PCT)application no. PCT/EP2013/068738, filed Sep. 10, 2013, and designatingthe US, which claims priority to U.S. provisional patent applicationNos. 61/699,488, filed Sep. 11, 2012, and 61/787,366, filed Mar. 15,2013.

FIELD OF THE INVENTION

The present invention relates to a method of cleansing the colon usingcolon cleansing solutions, and compositions and kits associatedtherewith. Colon cleansing compositions are also known as lavagesolutions, bowel cleansers, purgatives or colonic evacuants.

1. BACKGROUND

Colon or bowel cleansing is important before numerous surgical ordiagnostic procedures, including colonoscopy, barium enema examination,sigmoidoscopy and colon surgery. Such procedures are often carried outon an outpatient basis and thus it is desirable that the colon cleansingbe carried out by the patient at home, prior to arrival at the hospitalor surgery where the procedure is to take place. It is thereforeimportant that patient compliance is good without medical supervision ifsatisfactory colon cleansing is to be achieved prior to the procedure.

Intestinal lavage, in which a large volume of an aqueous electrolytesolution containing sodium sulphate and polyethylene glycol is ingested,is one of the most common methods for colon cleansing. These osmoticallyactive agents are non-absorbable or only poorly absorbable and thusretain water in the bowel, resulting in copious diarrhoea and cleansingof the colon.

For effective cleansing, many of these compositions must be ingested inquantities of between 2 to 4 litres. The unpleasant taste of thesecompositions combined with the large volumes required to be ingestedoften contributes to nausea or vomiting, resulting in poor patientcompliance and failure to consume the full volume of solution. Poorpatient compliance can lead to inadequate preparation of the colon whichcan, in turn, lead to cancellation or repetition of the colonoscopybecoming necessary or, worse, non-detection of lesions or polypsindicative of cancer risk.

A number of improved colon cleansing compositions are described in WO2004/037292. A colon cleansing composition according to WO 2004/037292that comprises polyethylene glycol 3350, sodium sulphate, an ascorbatecomponent, electrolytes, sweetener and flavouring is commercialised as apowder for oral solution under the tradename MOVIPREP® (registeredtrademark of Velinor AG, a member of the Norgine group of companies).The MOVIPREP solution is effective despite being taken in asubstantially lower volume than other colon cleansing solutions.Typically, only 2 litres of the solution need to be taken by an adultpatient (along with additional clear fluid), a significant benefit whencompared to taking 4 litres of previous solutions.

A recent advance in colon cleansing agents is provided by the productmarketed as SUPREP by Braintree Laboratories, Inc. SUPRPEP contains 17.5g sodium sulphate, 3.13 g potassium sulphate and 1.6 g magnesiumsulphate and it is taken in a volume of 16 US fluid ounces (473 ml). Atreatment comprises two doses of that solution.

Various regimens for the timing of ingestion of colon cleansingsolutions are mentioned in the literature and in patient informationleaflets that accompany colon cleansing products. For example, theMOVIPREP solution mentioned above may be taken (optionally withadditional clear liquids also being taken) in the evening before theexamination or procedure, or the MOVIPREP solution may be taken in a“split-dose” regimen, with approximately half of the cleansing solutionbeing taken the evening before the examination or procedure (“firstdose”), and the remainder being taken the following morning (“seconddose”). Similarly, the SUPREP product mentioned above is recommended tobe taken as first dose in the evening before the examination procedure,accompanied by an additional quart of water (946 ml), followed by asecond dose in the morning of the procedure.

An alternative to the lavage solutions described above is provided bylow volume hypertonic salt solutions. Examples include Fleet'sphosphosoda product and sodium picosulphate solutions. These are veryconcentrated salt solutions and patients need ingest only a small volumeof them (around 100 ml). However, these products have been associatedwith a hypo-osmolar state and electrolyte imbalance in subjects,particularly hyponatremia. They are particularly counter-indicated insubjects with kidney problems.

Despite the advances that have been made, all lavage-type coloncleansing products on the market continue to require a subject to ingesta large volume of solution (2 litres in the case of the MOVIPREPsolution). Many subjects find the ingestion of a large volume unpleasantor difficult and poor patient compliance thus remains a problem. Thereremains a need for alternative colon cleansing solutions that areeffective when ingested in small volumes, but do not cause electrolyteimbalances in subjects. There also remains a need for colon cleansingsolutions that are more pleasant to subjects to ingest, whilst retaininggood cleansing effectiveness.

2. SUMMARY OF THE INVENTION

The invention provides, in a first aspect, a colon cleansing solutioncomprising:

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid    -   the components (i) and (ii) being present in a molar ratio of        from 1:4.5 to 1:7.0; and

b) 10 to 200 g per litre polyethylene glycol.

The solution of the invention has a surprisingly palatable taste. Theparticular ratio of ascorbic acid to salt of ascorbic acid enables thesalty taste of ascorbate salt to be balanced by sourness from acid to apalatable extent, whilst at the same time not reducing the osmoticeffect of the ascorbate component or making the solution too sour. Thesolution is highly effective as a colon cleansing solution when ingestedin a lower volume than many prior art solutions, and it has a goodtolerability profile.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the results of the taste testing of thesolutions set forth in Table 1 herein.

FIG. 2 is a graph showing the results of the taste testing of thesolutions set forth in Table 2 herein.

FIG. 3 is a graph showing the results of the taste testing of thesolutions set forth in Table 3 herein.

FIG. 4 is a graph showing the results of the taste testing of thesolutions set forth in Table 4 herein.

3. DETAILED DESCRIPTION a) Contents of Solutions

The solutions of the invention are aqueous solutions. The mixture ofascorbic acid and one or more salts of ascorbic acid will, forconvenience, be referred to herein as the “ascorbate component”.Suitable salts of ascorbic acid include alkali metal salts and alkalineearth metal salts. For example, a salt may be selected from sodium,potassium, magnesium and calcium salts. For example, preferred salts ofascorbic acid include sodium ascorbate, potassium ascorbate, magnesiumascorbate and calcium ascorbate. The molar ratio between (i) theascorbic acid and (ii) the one or more salts of ascorbic acid is themolar ratio of the ascorbate moieties; for example, magnesium ascorbatecomprises two moles of ascorbate per mole of salt; for the ratiopurposes, it is the number of moles of ascorbate that is counted.Particularly preferred salts of ascorbic acid are magnesium ascorbateand sodium ascorbate, for example sodium ascorbate. In one embodiment,the solution comprises ascorbic acid and sodium ascorbate (andpreferably no further ascorbate).

Preferably, the molar ratio of the components (i) and (ii) is from1:4.75 to 1:6.75; more preferably from 1:5.0 to 1:6.0; for example from1:5.40 to 1:5.80; for example 15:85.

The solution of the invention preferably comprises ascorbate anion in aconcentration of: 300-700 mmol per litre, for example 350-650 mmol perlitre, for example 450-600 mmol per litre.

A solution of the invention may comprise 50 to 140 g/litre of ascorbatecomponent. For example, a solution of the invention comprises 60 to 140g/litre, for example 80 to 130 g/litre, for example 80 to 120 g/litre,for example 100 to 120 g/litre of ascorbate component.

Ascorbic acid has a molecular weight of 176 g/mol. Sodium ascorbate hasa molecular weight of 198 g/mol. Accordingly, a mixture of ascorbic acidand sodium ascorbate in a molar ratio of from 1:4.5 to 1:7.0 hasascorbic acid and sodium ascorbate present in a weight ratio of 1:5.063to 1:7.875. For example, the weight ratio can be 1:5.344 to 1:7.594;more preferably from 1:5.625 to 1:6.75; for example from 1:6.075 to1:6.525, for example 1:6.38. For example, a solution of the inventionmay comprise from 6 to 25 g/litre of ascorbic acid and 50 to 120 g/litreof sodium ascorbate, for example 12 to 20 g/litre of ascorbic acid and80 to 120 g/litre of sodium ascorbate (with the ratio between them beingas mentioned above). For example, a solution of the invention maycomprise from 14 to 16 g g/litre of ascorbic acid and 92 to 100 g/litreof sodium ascorbate.

Potassium ascorbate has a molecular weight of 214 g/mol. Accordingly, amixture of ascorbic acid and potassium ascorbate in a molar ratio offrom 1:4.5 to 1:7.0 has ascorbic acid and potassium ascorbate present ina weight ratio of 1:5.471 to 1:8.511. For example, the weight ratio canbe 1:5.776 to 1:8.208; more preferably from 1:6.080 to 1:7.295; forexample from 1:6.565 to 1:7.052, for example 1:6.896. For example, asolution of the invention may comprise from 6 to 25 g/litre of ascorbicacid and 50 to 125 g/litre of potassium ascorbate, for example 6 to 12g/litre of ascorbic acid and 80 to 120 g/litre of potassium ascorbate.

Magnesium ascorbate has a molecular weight of 374.5 g/mol and each moleof magnesium ascorbate provides two moles of ascorbate. Accordingly, amixture of ascorbic acid and magnesium ascorbate in a molar ratio offrom 1:4.5 to 1:7.0 (of ascorbate anion) has ascorbic acid and magnesiumascorbate present in a weight ratio of 1:4.794 to 1:7.457. For example,the weight ratio can be 1:5.061 to 1:7.191; more preferably from 1:5.326to 1:6.397 for example from 1:5.753 to 1:6.179, for example 1:6.042. Forexample, a solution of the invention may comprise from 6 to 25 g/litreof ascorbic acid and 45 to 120 g/litre of magnesium ascorbate, forexample 6 to 12 g/litre of ascorbic acid and 75 to 115 g/litre ofmagnesium ascorbate.

Depending on the pH of the solution, some ascorbate anion may beprotonated and thus exist as free ascorbic acid in solution. At the pHof solutions that would typically be administered, only a very minorproportion of ascorbate is protonated. In calculations of concentrationsof “ascorbate anion” herein, the concentration of “ascorbate anion” istaken as the total concentration of all ascorbate anion present,including the proportion that is protonated.

The cleansing solution comprises polyethylene glycol. The polyethyleneglycol (PEG) may, for example, have an average molecular weight of 2000to 8000, for example 2500 to 4500 Da, for example 2680 to 4020 Da, forexample 3000 to 4000 Da. For example, the PEG may be PEG 3350 or PEG4000 as defined in national pharmacopeias. PEG8000 may also be used.Further examples of suitable PEGs recognized in some nationalpharmacopeias include Macrogols, for example Macrogol 3350 or Macrogol4000.

The cleansing solution comprises 10 to 200 g per litre of PEG.Preferably, the solution comprises 20 to 160 g per litre of PEG, morepreferably 40 to 120 g per litre, for example 60 to 100 g per litre, forexample 75 to 85 g per litre, for example 80 g per litre.

The cleansing solution may additionally comprise one or more of:

c) one or more electrolytes;

d) one or more alkali metal or alkaline earth metal sulphates;

e) one or more flavouring agents;

f) one or more sweeteners.

The cleansing solution may comprise one or more electrolytes.Electrolytes include salts of sodium, potassium, calcium and magnesium,particularly sodium and potassium; and salts of chloride, iodide,bicarbonate and carbonate, particularly chloride. Preferred electrolytesare sodium chloride and potassium chloride. In an embodiment, thesolution is essentially free from sodium bicarbonate, for exampleessentially free from any bicarbonate.

For example, the solution may comprise sodium chloride at aconcentration of 1 to 10 g per litre. For example, sodium chloride maybe present at a concentration of 3 to 8 g per litre, for example 4 to 7g per litre; for example 6.0 to 6.8 g per litre; for example 5.6 g perlitre or 6.4 g per litre.

For example, the solution may comprise potassium chloride at aconcentration of 1 to 10 g per litre. For example, potassium chloridemay be present at a concentration of 1 to 7 g per litre, for example 1.5to 5 g per litre, for example 1.5 to 3 g per litre, for example 2.0 to2.8 g per litre; for example 2.4 g per litre or 2.6 g per litre.

In an embodiment, the solution comprises sodium chloride and potassiumchloride. They can be present in the amounts mentioned immediatelyabove. For example, sodium chloride may be present at a concentration of4 to 7 g per litre and potassium chloride may be present at aconcentration of 1.5 to 3 g per litre.

The cleansing solution may comprise one or more alkali metal sulphates,alkaline earth metal sulphates or a mixture thereof (herein referred toas a “sulphate component”). An alkali metal or alkaline earth metalsulphate may, for example, be selected from sodium sulphate, potassiumsulphate and magnesium sulphate. The solution may comprise more than oneof sodium sulphate, potassium sulphate and magnesium sulphate, forexample all three. Preferably, the sulphate component is or includessodium sulphate.

For example, the solution may comprise a sulphate component at aconcentration of 2 to 20 g per litre, for example 5 to 15 g per litre,for example 8 to 15 g per litre, for example 10 to 14 g per litre, forexample 12 g per litre. The one or more sulphate salts may be providedin any pharmaceutically acceptable form: they may each be anhydrous, orbe in a hydrated form. The weights mentioned herein refer to the weightof the sulphate salt excluding any water of hydration.

In an alternative preferred embodiment, the solution does not comprise asulphate component; that is to say that the solution is essentially freefrom alkali metal sulphates and alkaline earth metal sulphates; inparticular essentially free from sodium sulphate, potassium sulphate andmagnesium sulphate.

Herein, the term “essentially free from” a component means that thenamed component is present at a level that is below the level that hasany functional effect in the solution of the invention in its use; forexample, the named component may be at a level that is below the levelat which it has a measurable clinical effect. For example, it may meanthat the component is present at a level of less than 0.1 g per litre;for example less than 0.03 g per litre; for example less than 0.01 g perlitre, for example less than 0.003 g per litre, for example less than0.001 g per litre.

In the solutions of the invention described herein, the quantities ofthe individual components recited do not include any solutes that may bepresent in the water used to prepare the solutions, for example, in hardwater areas there may be significant amounts of Ca²⁺ and Mg²⁺carbonates, bicarbonates or sulphates present in tap water.

The cleansing solution preferably includes a flavouring agent. Aflavouring for use in compositions of the invention should preferablymask saltiness, be relatively sweet but not excessively so, and bestable in the composition. A flavouring makes the solutions morepalatable and thus aids patient compliance. Preferred flavouringsinclude lemon e.g. Ungerer Lemon (available from Ungerer Limited,Sealand Road, Chester, England CH1 4LP), strawberry e.g. UngererStrawberry, grapefruit e.g. Ungerer Grapefruit flavouring powder,blackcurrant e.g. Ungerer Blackcurrant, pineapple e.g. IFF(International Flavours and Fragrances) Pineapple flavouring powder,orange eg Firmenich Orange, vanilla/lemon and lime e.g. IFF Vanilla andGivaudin Roure Lemon and Lime Flav-o-lok, fruit punch eg Ungerer fruitpunch, citrus punch, mango, and berry. Those and further suitableflavourings are available from International Flavours and FragrancesInc. (Duddery Hill, Haverhill, Suffolk, CB9 8LG, England), Ungerer &Company (Sealand Road, Chester, England CH1 4LP) or Firmenich (FirmenichUK Ltd., Hayes Road, Southall, Middlesex UB2 5NN). More preferredflavourings are lemon, kiwi, strawberry, grapefruit, orange, fruit punchand mango. Citrus flavour, orange grapefruit flavour and orange flavourare particularly preferred.

The amount of flavouring required depends on the nature and strength ofthe flavouring in question. Typically, it is 0.05 to 4.5 g per litre,for example 0.05 to 2.0 g per litre, for example 0.2 to 1.8 g per litre,for example 1.0 to 1.8 g per litre, for example 3.0 to 4.5 g per litre,for example 0.3 g per litre or 1.2 g per litre, for example 3.2 or 4.2 gper litre.

The cleansing solution preferably includes a sweetener. Sugar-basedsweeteners are generally not suited for colon cleansing compositionsbecause the delivery of unabsorbed sugars to the colon provides asubstrate for bacteria. Such sugars may be metabolised by the bacteriato form explosive gases such as hydrogen and methane. The presence ofexplosive gases in the colon can be highly dangerous when electricalapparatus is to be used during colonoscopy or other procedures.Preferred sweeteners include aspartame, acesulfame potassium (acesulfameK), sucralose and saccharine, and/or combinations thereof. For example,compositions of the invention may comprise one or both of aspartame andacesulfame potassium (acesulfame K). For example, compositions of theinvention may comprise one or both of sucralose and acesulfame potassium(acesulfame K). In a preferred embodiment, the solution comprisesaspartame or sucralose, for example aspartame.

Alternatively, compositions of the invention can be essentially freefrom added sweeteners, for example to minimize the number of differentcomponents in the compositions.

A souring agent (for example citric acid) may be present as a tasteenhancer. A souring agent is a component that imparts a sourness to acomposition. Other souring agents include malic acid, acetic acid,tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid,phytic acid, lactic acid or salts thereof. The souring agent (forexample citric acid) may be provided in an encapsulated form. Theencapsulation provides a coating that isolates the souring agent fromother components and from air and moisture prior to its use. Severalencapsulated forms of citric acid, or other souring agents, arecommercially available. For example, the encapsulation may be with awater-soluble coating.

The amount of sweetener required depends on the nature and strength ofthe sweetener being considered. Typically, it is 0.10 to 4 g per litre.For example, the sweetener may be aspartame at 0.5 to 4 g per litre, forexample 2.5 to 4.0 g per litre, for example 3.0 g per litre, for example3.86 g per litre. Those quantities of aspartame are particularlysuitable when used with orange flavouring, for example orange flavouringat 0.2 to 1.8 g per litre, for example 1.0 to 1.8 g per litre, forexample 0.3 g per litre, 0.875 g per litre or 1.2 g per litre. Forexample, the sweetener may be aspartame at 1.0 to 2.5 g per litre, forexample 1.5 to 2.0 g per litre, for example 1.75 g per litre.

The invention thus provides a colon cleansing solution comprising:

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid    -   the components (i) and (ii) being present in a molar ratio of        from 1:4.5 to 1:7.0;

b) 10 to 200 g per litre PEG.

c) one or more electrolytes;

d) optionally one or more alkali metal or alkaline earth metalsulphates;

e) optionally one or more flavouring agents; and

f) optionally one or more sweeteners.

It will be apparent to the reader of this specification, that the term“comprising” and grammatical variations thereof, in relation toembodiments of the invention described, may be substituted in all cases(unless the context dictates otherwise) with the term “consistingessentially of” or “consisting of”. In the case of a solution that“consists of” or “consists essentially of” the stated components, thebalance is in each case made up of water.

In particular, the invention provides a colon cleansing solutioncomprising:

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid    -   the components (i) and (ii) being present in a molar ratio of        from 1:4.5 to 1:7.0;

b) 10 to 200 g per litre PEG having an average molecular weight of 3000to 4000 Da;

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents; and

f) optionally one or more sweeteners.

Each of c) and d) may be present in the concentrations described above.Each of e) and f) may be as described above and/or be in theconcentrations described above.

In particular, the invention provides a colon cleansing solutioncomprising:

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid    -   the components (i) and (ii) being present in a molar ratio of        from 1:4.5 to 1:7.0;

b) 10 to 200 g per litre PEG having an average molecular weight of 3000to 4000 Da;

c) sodium chloride and potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

In one embodiment, one or more components of c), d) (when present), e)and f) are present in the solution. In an alternative presentation, someor all of components c), d) (when present), e) and f) may be providedseparately from the solution, for example in a tablet or capsule. Forexample, components c) and d) may be provided in tablet form. In anembodiment, the solution may comprise a) the ascorbate component and b)PEG, and optional flavouring and sweetener (e) and f)), and a tablet orcapsule may comprise c) the one or more electrolytes (optionally withd), the one or more alkali metal or alkaline earth metal sulphates),again with optional flavouring and sweetener (e) and f). The flavouringand sweeteners need not be the same in the tablet or capsule as in thesolution.

In one embodiment, the invention provides a colon cleansing solutioncomprising:

a)

-   -   (i) 12 to 20 g per litre ascorbic acid and    -   (ii) 80 to 120 g per litre sodium ascorbate    -   the components (i) and (ii) being present in a weight ratio of        from 1:5063 to 1:7.875;

b) 60 to 100 g per litre PEG having an average molecular weight of 3000to 4000 Da;

c) 3 to 8 g per litre sodium chloride and 1 to 7 g per litre potassiumchloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

In an embodiment, the solution consists essentially of those components;that is to say that it does not contain any further components insignificant quantities. The solution may, for example, not contain anysulphate.

For example, the invention provides a colon cleansing solutionconsisting essentially of:

a)

-   -   (i) 14 to 16 g per litre ascorbic acid and    -   (ii) 92 to 100 g per litre sodium ascorbate

b) 75 to 85 per litre PEG having an average molecular weight of 3000 to4000 Da;

c) 6.0 to 6.8 g per litre sodium chloride and 2.0 to 2.8 g per litrepotassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

For example, the invention provides a colon cleansing solutionconsisting essentially of:

a)

-   -   (i) 15.08 g per litre ascorbic acid and    -   (ii) 96.22 g per litre sodium ascorbate

b) 80 g per litre PEG having an average molecular weight of 3000 to 4000Da;

c) 6.4 g per litre sodium chloride and 2.4 g per litre potassiumchloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

For example, the flavouring and sweetener may be 1.20 g per litre orangeflavour and 3.86 g per litre aspartame. For example, the flavouring andsweetener may be 3.20 g per litre citrus flavour and 1.75 g per litreaspartame. For example, the flavouring and sweetener may be 4.20 g perlitre orange grapefruit flavour and 1.75 g per litre aspartame.

Preferably, the colon cleansing solution is hyper-osmotic. That is tosay that it has a higher osmotic strength than blood in the human body.It may, for example have a measured osmolality in the range 500 to 2000mOsmol/kg. For example, the osmolality may be in the range 700 to 1800mOsmol/kg.

For example, the solutes in 500 ml of the solution may have a measuredV(350) value of from 1000 to 2000 ml, for example from 1300 to 2000 ml,for example from 1400 to 1900 ml, and be in a volume of 400 to 600 ml,for example 500 ml. The V(350) value is the volume of water that isrequired to provide a solution with an osmolality of 350 mOsmol/kg, thetotal volume being the final volume after a volume water has been addedto a solution having an initial volume.

Osmolality can be measured in various ways. In general, either freezingpoint depression or vapour-pressure alteration is used. For example, anAdvanced Instruments, Inc Model 3250 osmometer (a freezing pointdepression device) can be used. Vapour pressure measurement can also beused, for example using an ELITech Group Vapro 5600 device. Osmolalityvalues cited herein are preferably taken to be values measured using afreezing point depression osmometer, for example using an AdvancedInstruments, Inc Model 3250 osmometer following standard operatingprocedure.

The invention provides a colon cleansing solution comprising:

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid    -   the components (i) and (ii) being present in a molar ratio of        from 1:4.5 to 1:7.0; and

b) 10 to 200 g per litre PEG having an average molecular weight of 3000to 4000 Da;

and 500 ml of the solution having a V(350) osmolality value of from 1300to 2300 ml.

For example, 500 ml of the solution may have a V(350) osmolality valueof from 1500 to 2100 ml, for example from 1700 to 2000 ml, for examplefrom 1800 to 1900 ml.

b) Additional Optional Contents of Solutions

Unless it is stated otherwise, the solutions of the invention mayinclude one or more additional optional components:

(i) antioxidants

In general it is not necessary for the solutions to includepreservatives or anti-oxidants. Nevertheless, low levels ofanti-oxidants or preservatives may be used if required.

(ii) laxatives

In general, the solutions described herein are effective without theneed for any additional active ingredients. Nevertheless, a furtheractive ingredient may be included if required. For example, a laxativemay be present, for example a stimulant laxative. For example,bisacodyl, castor oil, senna or bisoxatin may be used. An example of acolon cleansing solution containing bisoxatin is known fromWO2013001315.

(iii) Contrast Media

For certain uses, one or more contrast media can be included in asolution of the invention. Examples of contrast media include barium oriodine products, diatrizoate (marketed, for example, as HYPAQUE 50),metrizoate (marketed, for example, as ISOPAQUE 370), ioxalgate(marketed, for example, as HEXABRIX), iopamidol (marketed, for example,as ISOVUE 370), iohexol (marketed, for example, as OMNIPAQUE 350),ioxilan (marketed, for example, as OXILAN 350), iopramide (marketed, forexample, as ULTRAVIST 370), iodixanol (marketed, for example, asVISIPAQUE 320) and/or a diatrizoic acid or its anionic form diatrizoate(also known as amidotrizoic acid, or3,5-diacetamido-2,4,6-triiodobenzoic acid; marketed, for example, asHYPAQUE). Alternatively, the solution of the invention may be used inconjunction with (e.g., simultaneously, before or after) administrationof a contrast agent or contrast media.

(iv) Dyes and Stains.

For certain uses (eg fluorescence endoscopy), one or more dyes or stainsthat are markers of particular mucosal pathology can be included in asolution of the invention. Stains may be selective. For example,hexaminolevulinate may be used, for example as its HCl salt (marketed asCYSVIEW). Other markers of colonic or rectal mucosal pathology can beused. For example methylene blue, which can stain the normal mucosa yetpolyps do not stain and become more clearly visible.

Further dyes and stains that may be mentioned include: Curcumin,Riboflavin, Riboflavin-5′-phosphate, Tartrazine, Quinoline Yellow,Sunset Yellow, FCF Orange, Yellow S, Cochineal, Carminic acid, Carmines,Azorubine, Carmoisine, Ponceau 4R, Cochineal Red A, Allura Red AC,Patent Blu EV, Indigotine, Indigo carmine, Brilliant Blue FCF,Chlorophylls and chlorophyllins, Copper complexes of chlorophylls andchlorophyllins, Green S, Plain caramel, Brilliant Black BN, Black PN,Vegetable carbon, Brown HT, Carotenes, Lutein, Beetroot Red, betanin,Anthocyanins, Calcium carbonate, Titanium dioxide, Iron oxides andhydroxides, Amaranth, Brown F, Erythrosine, Lithol Rubine B and/or Red2G. Further dyes and stains that may be mentioned include: acidfuchsine, Alba red, Alizarin cyanine green F, Alizurol purple S5, AlluraRed AC, Alphazurine FGBrilliant lake red R, Dibromofluorescein,Diiodofluorescein, Eosine, Erythrosine yellowish Na, Fast green FCF,Flaming red, Fluorescein, Helindone pink CN, Indanthrene blue, Lakebordeaux B, Lithol rubin B Ca, Naphthol yellow 5, Orange II, Phloxine B,Ponceau 5X, Pyranine concentrated, Quinizarinegreen 5S,Tetrabromo-fluorescein, Tetrachlorotetrabromo fluorescein, Toney red,Uranine, Alcian Blue, Anazolene Sodium, Brilliant Green, Cantaxanthin,Carthamin, Citrus Red 2, Evan's Blue, Fast Green FCF, lndocyanine Green,Methyl Blue, Methylene Blue, N-(p-Methoxyphenyl)-p-phenylenediamine,Ponceau 3R, Ponceau SX, Pyranine, Rhodamine B, Saunders Red, Sudan BlackB, Sulphan Blue, Tolonium Chloride, and/or Vital Red or equivalents orany combination thereof.

Alternatively, the solution of the invention may be used in conjunctionwith (e.g., simultaneously, before or after) administration of a dye orstain. A dye or a stain may be provided in slow or delayed release form,for example delayed release methylene blue (for example MMX format ofcolonic-released methylene blue) may be mentioned.

(v) Surfactants

A surfactant may be included in a solution of the invention. Asurfactant may assist in avoiding the persistence of bubbles in thecolon. Such bubbles can interfere with the visualisation of features ofthe colon during colonoscopy. Surfactants that may be mentioned includesimethicone (or any mixture of polydimethylsiloxane and silica gel),dimethicone. Bowel cleansing solutions containing simethicone aredescribed in WO2009052256.

(vi) Lubricants

A lubricant may be included in a solution of the invention. Theinclusion of a lubricant can help with a colonoscope insertion andfacilitation within the performance of the colonoscopy. Suitablelubricants include glycerol or silicone.

(vii) Biofilm-Disrupting Compounds

A biofilm disrupting compound may be included in a solution of theinvention. A compound that disrupts biofilms may assist in separating anadherent polysaccharide DNA-containing layer, the so-called “biofilm”from the colonic mucosa. Removal of that layer may assist in achieving acleaner and/or more easily visualized or stained mucosa.

Biofilm-disrupting components or agents that may be mentioned includeenzymes such as deoxyribonuclease (DNase), N-acetylcysteine, alginatelyase, glycoside hydrolase dispersin B; Quorum-sensing inhibitors e.g.,ribonucleic acid III inhibiting peptide, Salvadora persica extracts,Competence-stimulating peptide, Patulin and penicillic acid;peptides—cathelicidin-derived peptides, small lytic peptide, PTP-7 (asmall lytic peptide, see e.g., haridia (2011) J. Microbiol. 49(4):663-8,Epub 2011 Sep. 2), Nitric oxide, neo-emulsions; ozone, lyticbacteriophages, lactoferrin, xylitol hydrogel, synthetic iron chelators,cranberry components, curcumin, silver nanoparticles, Acetyl-11-keto-P-boswellic acid (AKBA), barley coffee components, probiotics,sinefungin, S-adenosylmethionine, S-adenosyl-homocysteine, Deliseafuranones, N-sulfonyl homoserine lactones and/or macrolide antibioticsor any combination thereof.

Alternatively, the solution of the invention may be used in conjunctionwith (e.g., simultaneously, before or after) administration of abiofilm-disrupting compound. A biofilm-disrupting compound may beadministered towards the end of ingestion of the solution of theinvention, or shortly after completion of ingestion of the solution ofthe invention, so as to disrupt the biofilm most just before thecolonoscopy.

(viii) Organic Acids

Some of the osmotic load of the solution of the invention may beprovided by an organic acid or salts of an organic acid other thanascorbic acid. For example, citric acid and/or salts thereof may replacesome or all of the ascorbate in solutions of the invention. Throughoutthis description, ascorbic acid may be replaced with citric acid. A saltof ascorbate may be replaced with the salt of citrate. Sodium citrate,potassium citrate and magnesium citrate are particularly preferred.

c) Uses of Solutions of the Invention

The solutions of the invention find use in cleansing the colon or bowel.They are also useful in the treatment of faecal impaction orconstipation.

When carrying out a bowel cleansing treatment, a subject typically takesa single dose or a split dose of cleansing solution. In a split-dosetreatment, typically two doses are taken separated by a time interval,for example an overnight interval. Alternatively, in a split-dosetreatment two doses may be taken on the same day, for example during theday before a therapeutic or surgical procedure, or during the day of atherapeutic or surgical procedure. Each dose in a split dose treatmentis smaller than the dose in the single dose treatment. In a split dosetreatment, the two doses may each have the same composition, or they maybe different.

For a single dose treatment, the solution of the invention may beingested in a volume of 700 to 1500 ml. For example, the subject mayingest from 750 ml to 1300 ml of the solution, for example 800 to 1200ml, for example 900 to 1100 ml, for example 1000 ml. For example 33 or34 US fluid ounces may be ingested. In an embodiment, the subject mayingest some additional clear fluid. The additional clear fluid may beingested after ingesting the solution. Alternatively, the additionalclear fluid may be co-administered with the intake of the solution ofthe invention. By “co-administered” is meant the coordinated ingestionof a solution of the invention with clear fluid; that is to say that thesubject ingests some of the solution of the invention but notnecessarily the whole dose, then some clear fluid and then more solutionof the invention.

For a split dose treatment, the solution of the invention may be takenas one or both of the doses, each dose having a volume of 200 to 1000ml. For example, the subject may ingest (as one of the doses) 300 ml to1000 ml of the solution, for example 300 ml to 900 ml, for example 300ml to 800 ml, for example 400 ml to 700 ml, for example 400 to 600 ml,for example 450 to 550 ml, for example 500 ml. For example 16 or 17 USfluid ounces may be ingested.

The combined volume of the first and second doses is preferably lessthan 2 litres. Preferably, it is 1750 ml or less, for example 1500 ml orless, for example 1250 ml or less. For most adult subjects, a combinedvolume of more than 500 ml is used, for example more than 750 ml. Forexample, a combined volume of from 500 ml to 1750 ml is used, forexample from 750 ml to 1500 ml, for example from 1000 ml to 1500 ml, forexample 1000 ml or 1250 ml. For example the first dose may have a volumeof 500 ml (for example a volume of 16 or 17 US fluid ounces) or 750 ml(for example a volume of 25 or 26 US fluid ounces) and the second dosemay have a volume of 500 ml (for example a volume of 16 or 17 US fluidounces).

In an embodiment, the subject may ingest some additional clear fluidwith each or either dose of colon cleansing solution. The additionalclear fluid may be taken after ingesting a dose of the solution.Alternatively, the additional clear fluid may be co-administered withthe intake of a dose of the solution of the invention; that is to saythat the subject ingests some of the solution of the invention but notnecessarily the whole dose, then some clear fluid and then more solutionof the invention.

In the method, there is typically a time interval between ingesting thefirst dose and ingesting the second dose. Generally, the time intervalis at least 4 hours, for example 6 hours or more, for example 8 hours ormore. Typically, the time interval is less than 15 hours. The timeinterval between starting to take the first dose and starting to takethe second dose may be, for example, the time between an evening and thefollowing morning, for example 12 to 16 hours, for example 14 hours. Forexample, the subject may sleep (for example overnight) between takingthe first and second doses.

Alternatively, the time interval between ingesting the first dose andingesting the second dose can be at least 10 minutes, for example from10 minutes to 4 hours, for example from 30 minutes to 4 hours, forexample from 30 minutes to two hours. For example, the subject mayingest the first and second colon doses the evening before a surgical ordiagnostic procedure. The time interval between ingesting the firstsolution and ingesting the second solution can be determined by the timeit takes for the subject to experience a bowel movement. For example thesubject takes the second dose when the first bowel movement has occurredafter completing ingestion of the first solution. Alternatively, thesubject ingests the second dose when the first bowel movement hasoccurred even if ingestion of the first dose is not complete.

During the ingestion of the first or second dose, or during the timeinterval between the ingestion of the first dose and the second dose,the subject may additionally take a stimulant laxative (also known as aprokinetic agent). A stimulant laxative can assist in bringing aboutgood cleansing. Examples of stimulant laxatives include contactlaxatives, for example bisacodyl, castor oil, senna or bisoxatin.Examples of stimulant laxatives also include additional osmotic agentsfor example magnesium salts, for example magnesium citrate. If astimulant laxative is included in the regimen, the length of the timeinterval can be shortened. For example, it may be 10 minutes to 15hours, for example 1 to 15 hours, for example 1 to 12 hours, for example2 to 10 hours.

During the time interval between the administration of the first doseand the second dose, it is very likely that the subject will experiencea bowel movement. Advantageously, the subject waits until the bowelmovement has occurred before taking the second dose.

In a split dose treatment, the solution of the invention may be takenfor one or for both of the doses. Preferably, the solution of theinvention is taken as the second solution. For example, the subject mayingest 300 ml to 1000 ml of the solution of the invention as the secondsolution, for example 300 ml to 900 ml, for example 300 ml to 800 ml,for example 400 ml to 700 ml, for example 400 to 600 ml, for example 450to 550 ml, for example 500 ml. For example 16 or 17 US fluid ounces maybe ingested.

The first solution may be a solution of different constitution from thesecond solution. Thus, in a preferred embodiment of a split dose bowelcleansing treatment, a subject takes a dose of an initial cleansingsolution, optionally followed by some additional clear fluid. After aninterval, the subject then takes a dose of the solution of theinvention, optionally followed by some additional clear fluid.

The volume of clear fluid that a subject ingests after the first orsecond dose may be in a range with a lower limit of 100 ml, 200 ml, 300ml, 400 ml or 500 ml. Preferably, the lower limit is 300 ml, 400 ml or500 ml. The volume may be in a range with an upper limit of 1200 ml,1100 ml, 1000 ml, 900 ml or 800 ml. For example the volume may be in therange 100 ml to 1200 ml, for example 200 ml to 1100 ml, for example 300ml to 1000 ml, for example 500 ml to 900 ml, for example 1000 ml, forexample 875 ml, for example 500 ml to 800 ml. For example the volume maybe in the range 300 ml to 900 ml, for example 400 ml to 800 ml, forexample 500 ml to 800 ml. The additional clear fluid may be ingested ina volume of at least 500 ml. For example it may be at least 16 or 17 USfluid ounces. The instructions provided to the subject may suggest thatthe additional clear fluid is ingested over a period of approximatelyone hour, for example in 150 to 200 ml fractions every 15 to 20 minutes.The additional clear fluid may be taken after taking a dose of thesolution. Alternatively, the additional clear fluid may beco-administered with the intake of a dose of the solution of theinvention; for example, the subject may ingest clear fluid betweenfractions of the solution of the invention; for example the subject mayingest a cup of the solution of the invention, followed by a cup ofclear fluid, followed by further cups of the solution of the invention.

A clear fluid for taking as the additional clear fluid, or for use asthe clear fluid when making up a solution, may be any fluid that allowsinspection of colonic output. The clear fluid should also not impedeinspection of the colon during the colonoscopy. Typically the clearfluid is a water-based beverage, including, for example, water,lemonade, cola drinks, cordial drinks, clear fruit juices and even clearalcohol-containing beverages, for example beer. It is desirable that theclear fluid does not contain substantial amounts of or essentially anydietary fibre, as such fibre interferes with the cleansing of the colonaccording to the present invention. Accordingly, fruit juices, forexample orange juice and kiwi juice, and fruit “squashes” should bestrained before use. Clear fruit cordials, for example lime cordial ortea (for example green tea), are generally suitable. In view of thedesirability of avoiding drinks containing glucose, so as to reduce therisk of explosive concentrations of hydrogen or methane building up inthe gut, “diet” drinks containing no or low sugar are especiallysuitable, for example liquid drinks for diabetics, diet Coke®, dietlemonade, dietary carbonated drinks or dietary cordials. The mostpreferred clear fluid is water.

The method of the invention may be used to cleanse the colon prior tocarrying out a diagnostic, therapeutic or surgical procedure on thecolon, rectum or anus or elsewhere in the abdomen in a subject. Thesubject is most preferably a human. The diagnostic or surgical proceduremay, for example, be colonoscopy (such as cap-assisted colonoscopyand/or narrow-band colonoscopy), barium enema examination, sigmoidoscopy(for example flexible sigmoidoscopy) or colon surgery. The method of theinvention may be a method of cleansing the colon prior to a surgical ordiagnostic procedure comprising administering the first solution andthen after a time interval administering the second solution prior tosaid procedure.

The solutions, compositions and kits described herein also find use inthe treatment of constipation and faecal impaction. They also find usein the treatment of severe bacterial infections of the bowel. Theinvention thus provides solutions, compositions and kits as describedherein for use in the treatment of constipation or faecal impaction, orin the treatment of severe bacterial infections of the bowel. Theinvention also provides methods of treating constipation or faecalimpaction, or in the treating severe bacterial infections of the bowelcomprising administration of solutions as described herein.

As mentioned above, the solutions of the invention find use in cleansingthe colon. The invention provides, in a further aspect, a solution inwater of:

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) optionally 10 to 200 g per litre polyethylene glycol,

for use in cleansing the colon of a mammal.

The solution for use in cleansing the colon of a mammal preferablycomprises ascorbate anion in a concentration of: 300-700 mmol per litre,for example 350-650 mmol per litre, for example 450-600 mmol per litre.As set out above, the ascorbate anion is provided by a mixture ofascorbic acid and one or more salts of ascorbic acid. Preferred forms ofthe ascorbate component are as set out above in section 3a).

In a preferred embodiment, PEG is present. Preferred forms of the PEGand preferred amounts thereof are as set out above in section 3a).

The solution for use in cleansing the colon of a mammal may additionallycomprise one or more of:

c) one or more electrolytes;

d) one or more alkali metal or alkaline earth metal sulphates;

e) one or more flavouring agents;

f) one or more sweeteners.

For example, the solution for use in cleansing the colon of a mammaladditionally comprises elements c), e) and f) from that list.

Preferred electrolytes and preferred amounts thereof are as set outabove in section 3a).

Preferred alkali metal or alkaline earth metal sulphates and preferredamounts thereof are as set out above in section 3a).

Preferred flavouring agents and preferred amounts thereof are as set outabove in section 3a).

Preferred sweeteners and preferred amounts thereof are as set out abovein section 3a).

For example, the solution in water comprises:

a) 150 to 400 mmol ascorbate anion, provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) optionally 5 to 100 g PEG.

In particular, the invention provides a solution comprising:

a) 150 to 400 mmol ascorbate anion, provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid    -   the components (i) and (ii) being present in a molar ratio of        from 1:4.5 to 1:7.0;

b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da;

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents; and

f) optionally one or more sweeteners

for use in cleansing the colon of a mammal.

Each of c) and d) may be as described above and/or be present in theamounts described above in section 3a). Each of e) and f) may be asdescribed above and/or be in the amounts described above section 3a).

In particular, the invention provides a solution consisting essentiallyof:

a)

-   -   (i) 14 to 16 g per litre ascorbic acid and    -   (ii) 92 to 100 g per litre sodium ascorbate

b) 75 to 85 per litre PEG having an average molecular weight of 3000 to4000 Da;

c) 6.0 to 6.8 g per litre sodium chloride and 2.0 to 2.8 g per litrepotassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners,

for use in cleansing the colon of a mammal.

Each of c) and d) may be as described above and/or be present in theamounts described above in section 3a). Each of e) and f) may be asdescribed above and/or be in the amounts described above section 3a).

For example, the invention provides a solution consisting essentiallyof:

a)

-   -   (i) 15.08 g per litre ascorbic acid and    -   (ii) 96.22 g per litre sodium ascorbate

b) 80 g per litre PEG having an average molecular weight of 3000 to 4000Da;

c) 6.4 g per litre sodium chloride and 2.4 g per litre potassiumchloride;

e) one or more flavouring agents; and

f) one or more sweeteners,

for use in cleansing the colon of a mammal.

For example, the flavouring and sweetener may be 1.20 g per litre orangeflavour and 3.86 g per litre aspartame. For example, the flavouring andsweetener may be 3.20 g per litre citrus flavour and 1.75 g per litreaspartame. For example, the flavouring and sweetener may be 4.20 g perlitre orange grapefruit flavour and 1.75 g per litre aspartame.

As mentioned above, a bowel cleansing treatment typically involves asubject taking a single dose or a split dose of cleansing solution. Thevolume of solution that a subject takes in a single dose treatment isdescribed hereinabove. The subject may take some additional clear fluidafter taking the solution as described hereinabove. The volume ofsolution that a subject takes in a split dose treatment is describedhereinabove. The subject may take some additional clear fluid after eachor either dose the solution as described hereinabove.

d) Compositions for Preparing Doses of Solutions

The invention further provides a composition (for example a drycomposition, for example a powder) for the preparation of a solution ofthe invention. A composition can be in a quantity for the preparation ofa dose of the solution, for example a 500 ml dose (for example a 16 or17 US fluid ounce dose). The invention provides a composition foradmixture with water, wherein the composition is optionally presented intwo or more parts and comprises:

a) 150 to 400 mmol ascorbate anion provided by a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) 5 to 100 g polyethylene glycol.

For example, the components may be in dry powder, granular or other dryform. They may alternatively be in the form of concentrates or slurries.Components may be in the same or different physical forms. For example,the composition is a dry composition, for example a dry powdercomposition. For example, one or both of components a) and b) are drypowders. In a dry powder, it is possible for one or more components tobe a salt hydrate.

As set out above in section 3a), the ascorbate anion is provided by amixture of ascorbic acid and one or more salts of ascorbic acid.Preferred forms of the ascorbate component are as set out above inrelation to solutions of the invention.

The composition of the invention preferably comprises ascorbate anion inan amount of 150 to 350 mmol, for example 175-325 mmol, for example225-300 mmol

Ascorbic acid has a molecular weight of 176 g/mol and sodium ascorbatehas a molecular weight of 198 g/mol. Accordingly, the 150 to 400 mmolascorbate anion can be provided by 3.3 to 12.8 g ascorbic acid and 24.3to 69 g sodium ascorbate, for example 5.0 to 10 g ascorbic acid and 40to 60 g sodium ascorbate; for example 6.0 to 10 g ascorbic acid and 40to 60 g sodium ascorbate; for example 7.0 to 8.0 g ascorbic acid and 44to 52 g sodium ascorbate; for example 7.0 to 8.0 g ascorbic acid and 46to 50 g sodium ascorbate.

Potassium ascorbate has a molecular weight of 214 g/mol. Accordingly,the 150 to 400 mmol ascorbate anion can be provided by 3.3 to 12.8 gascorbic acid and 26 to 75 g potassium ascorbate, for example 5.0 to 10g ascorbic acid and 45 to 65 g potassium ascorbate; for example 7.0 to8.0 g ascorbic acid and 47 to 56 g sodium ascorbate.

Magnesium ascorbate has a molecular weight of 374.5 g/mol and each moleof magnesium ascorbate provides two moles of ascorbate. Accordingly, the150 to 400 mmol ascorbate anion can be provided by 3.3 to 12.8 gascorbic acid and 23 to 65 g magnesium ascorbate, for example 5.0 to 10g ascorbic acid and 38 to 57 g magnesium ascorbate; for example 7.0 to8.0 g ascorbic acid and 42 to 49 g magnesium ascorbate.

In solid form, ascorbic acid is typically made up of protonated freeascorbic acid. In calculations of concentrations of “ascorbate anion”herein, the number of moles of “ascorbate anion” is taken as the totalconcentration of all ascorbate anion present, including the proportionthat is protonated.

The weight of the ascorbate component may be 20 to 85 g, for example 25to 75 g, for example 20 to 60 g, for example 50 to 60 g.

In an embodiment, the ascorbate component comprises (or consistsessentially of) sodium ascorbate and ascorbic acid. For example, theymay be present in a total amount and in a weight ratio as mentionedimmediately above.

Preferred forms of the PEG are as set out above in section 3a), inrelation to solutions of the invention. The composition comprises 5 to100 g of PEG. Preferably, the composition comprises 10 to 80 g of PEG,more preferably 20 to 60 g, for example 30 to 50 g, for example 37.5 to42.5 g, for example 40 g of PEG.

The composition may additionally comprise one or more of:

c) one or more electrolytes;

d) one or more alkali metal or alkaline earth metal sulphates;

e) one or more flavouring agents; and

f) one or more sweeteners.

Preferred electrolytes are as set out above in section 3a), in relationto solutions of the invention. For example, the composition may comprisesodium chloride in an amount of 0.5 to 5 g, for example 1.5 to 4 g, forexample 2.0 to 3.5 g, for example 2.8 g or 3.2 g. For example, thecomposition may comprise potassium chloride in an amount of 0.5 to 5 g,for example 0.5 to 3.5 g, for example 0.75 to 2.5 g, for example 0.75 to1.5 g, for example 1.0 to 1.4 g, for example 1.2 g or 1.3 g. In anembodiment, the composition is essentially free from sodium bicarbonate,for example essentially free from any bicarbonate.

Preferred alkali metal or alkaline earth metal sulphates are as set outabove in section 3a), in relation to solutions of the invention. Forexample, the composition may comprise a sulphate component in an amountof 1 to 10 g, for example 2.5 to 7.5 g, for example 4 to 7.5 g, forexample 5 to 7 g, for example 6 g. The one or more sulphate salts may beprovided in any pharmaceutically acceptable form: they may each beanhydrous, or be in a hydrated form. The weights mentioned herein referto the weight of the sulphate salt excluding any water of hydration. Ahydrate form may be present in the dry powder composition, and thatcomposition is still considered “dry” herein. In an alternativepreferred embodiment, the composition does not comprise a sulphatecomponent; that is to say that the composition is essentially free fromalkali metal sulphates and alkaline earth metal sulphates; in particularessentially free from sodium sulphate, potassium sulphate and magnesiumsulphate.

Preferred flavouring agents are as set out above in section 3a), inrelation to solutions of the invention. For example the amount offlavouring agent may be 0.025 to 2.25 g, for example 0.025 to 1.0 g, forexample 0.1 to 0.9 g, for example 0.5 to 0.9 g, for example 1.5 to 2.25g, for example 0.15 g or 0.6 g, for example 1.6 or 2.1 g.

Preferred sweeteners are as set out above in section 3a), in relation tosolutions of the invention. The amount of sweetener required depends onthe nature and strength of the sweetener being considered. For examplethe amount of sweetener may be 0.05 to 2 g, for example 0.25 to 2 g, forexample 1.25 to 2 g, for example 1.5 g, for example 1.93 g. Thosequantities of aspartame are particularly suitable when used with orangeflavouring, for example orange flavouring at 0.1 to 0.9 g, for example0.5 to 0.9 g, for example 0.15 g, 0.4375 g or 0.6 g. For example, thesweetener may be aspartame at 0.5 to 1.25 g, for example 0.75 to 1.0 g,for example 0.875 g.

In particular, the invention provides a composition comprising:

a) 150 to 400 mmol ascorbate anion provided by a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid    -   the components (i) and (ii) being present in a molar ratio of        from 1:4.5 to 1:7.0;

b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da.

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents;

f) optionally one or more sweeteners.

Each of c) and d) may be present in the amounts described above. Each ofe) and f) may be as described above and/or be in the amounts describedabove.

In one embodiment, the invention provides a composition comprising:

a)

-   -   (i) 6.0 to 10 g ascorbic acid and    -   (ii) 40 to 60 g sodium ascorbate

the components (i) and (ii) being present in a weight ratio of from1:5063 to 1:7.875;

b) 30 to 50 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 1.5 to 4 g sodium chloride and 0.5 to 3.5 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

In one embodiment, the invention provides a composition comprising:

a)

-   -   (i) 7.43 g ascorbic acid and    -   (ii) 48.11 g sodium ascorbate

b) 40 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 3.20 g sodium chloride and 1.20 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

For example, the flavouring and sweetener may be 0.60 g orange flavourand 1.93 g aspartame. For example, the flavouring and sweetener may be1.60 g citrus flavour and 0.875 g aspartame. For example, the flavouringand sweetener may be 2.10 g orange grapefruit flavour and 0.875 gaspartame.

In an embodiment, the composition consists essentially of thosecomponents; that is to say that it does not contain any furthercomponents in significant quantities. The composition may, for example,not contain any sulphate.

One or more of components a) to f) may be presented in solid form, or insemi-solid form (for example in gel form).

In one embodiment, the one or more components of c), d) (when present),e) and f) are present in the composition for making up a solution. In analternative presentation, some or all of components c), d) (whenpresent), e) and f) may be provided separately from the composition formaking up the solution, for example in a tablet or capsule. In anembodiment, there may be provided the ascorbate component and PEG, andoptional flavouring and sweetener, in a form for admixture with water,and a tablet or capsule comprising the one or more electrolytes and/orthe one or more alkali metal or alkaline earth metal sulphates, againwith optional flavouring and sweetener. The flavouring and sweetenersneed not be the same in the tablet or capsule as in the composition foradmixture with water.

In some embodiments, it is desirable to package the ascorbate and thePEG components separately from each other.

In an embodiment, the composition can be provided to the subject with aplurality of flavouring agents (each optionally with one or moresweeteners), each separately packaged. The subject can then select apreferred flavouring (or flavouring and sweetener combination) accordingto his or her taste. The subject also has the choice of not using anyflavouring or sweetener at all.

It will be apparent to the reader that all compounds and compositionsdescribed herein are of a nature and quality suitable for mammalian(especially human) consumption. For example, they are of pharmaceuticalgrade. The pharmaceutically acceptable compositions described herein maybe provided in packaged form with instructions for use.

e) Compositions for Preparing Solutions

In a further aspect, the invention provides a composition comprising thefollowing components in the following weight ratios:

a) ascorbate anion 0.82 to 4.0 parts provided by a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) polyethylene glycol 1.0 part.

As mentioned above, for example, the components may be in dry powder,granular or other dry form. They may alternatively be in the form ofconcentrates or slurries. Components may be in the same or differentphysical forms. For example, the composition is a dry composition, forexample a dry powder composition. For example, one or both of componentsa) and b) are dry powders.

As set out above, the ascorbate anion is provided by a mixture ofascorbic acid and one or more salts of ascorbic acid. Preferred forms ofthe ascorbate component are as set out above in section 3a) in relationto solutions of the invention.

Preferred forms of the PEG are as set out above in section 3a) inrelation to solutions of the invention. The composition of the inventionpreferably comprises ascorbate anion in a weight ratio to PEG of 0.82 to3.0:1. More preferably, the weight ratio is 0.9 to 2.0:1, for example1.0 to 1.5:1, for example 1.2 to 1.3:1. As set out above, the ascorbateanion is provided by ascorbic acid and a salt of ascorbic acid in aratio of 1:4.5 to 1:7.0. The molar ratio of the ascorbic acid and theone or more salts of ascorbic acid is from 1:4.75 to 1:6.75; morepreferably from 1:5.0 to 1:6.0; for example from 1:5.40 to 1:5.80; forexample 15:85. The salt of ascorbic acid can be sodium ascorbate. Amixture of ascorbic acid and sodium ascorbate in a molar ratio of from1:4.5 to 1:7.0 has ascorbic acid and sodium ascorbate present in aweight ratio of 1:5.063 to 1:7.875. A more preferred ratio is 1:5.344 to1:7.594; more preferably from 1:5.625 to 1:6.75; for example from1:6.075 to 1:6.525, for example 1:6.38.

In a composition in which the weight ratio of ascorbate anion to PEG is0.82 to 3.0:1, and in which the ascorbate anion is provided by ascorbicacid and a sodium ascorbate in a molar ratio of 1:4.5 to 1:7.0, theweight ratio of ascorbic acid:sodium ascorbate:PEG is 0.1031 to0.5486:0.7591-2.970:1. For example, the weight ratio can be 0.12 to0.30:0.9 to 1.9:1; more preferably 0.15 to 0.25:1.0 to 1.5:1; forexample 0.185 to 0.190:1.15 to 1.25:1; for example 0.1885:1.203:1.

The composition may additionally comprise one or more of:

c) one or more electrolytes;

d) one or more alkali metal or alkaline earth metal sulphates;

e) one or more flavouring agents;

f) one or more sweeteners.

Preferred electrolytes are as set out above in section 3a) in relationto solutions of the invention. For example, the composition may comprisesodium chloride in a weight ratio to PEG of 0.005 to 0.5:1, for example0.01 to 0.3:1, for example 0.03 to 0.2:1, for example 0.04 to 0.15:1,for example 0.05 to 0.1:1, for example 0.06 to 0.09:1. For example, thecomposition may comprise potassium chloride in a weight ratio to PEG of0.005 to 0.30:1, for example 0.01 to 0.20:1, for example 0.01 to 0.10:1,for example 0.02 to 0.04:1.

For example, the invention provides a composition comprising thefollowing components in the following weight ratios:

a) ascorbate anion: 0.82 to 4.0 parts;

b) polyethylene glycol: 1.0 part;

c1) sodium chloride: 0.005 to 1.0 parts; and

c2) potassium chloride: 0.005 to 1.0 parts;

the ascorbate anion being provided by

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0.

The composition is preferably essentially free from sodium bicarbonate.For example, it is essentially free from any bicarbonate.

Preferred alkali metal or alkaline earth metal sulphates are as set outabove in section 3a) in relation to solutions of the invention. Forexample, the composition may comprise a sulphate component (for examplesodium sulphate) in a weight ratio to PEG of 0.01 to 0.50:1, Forexample, the composition may comprise a sulphate component (for examplesodium sulphate) in a weight ratio to PEG of 0.02 to 0.25:1, for example0.03 to 0.22:1, for example 0.05 to 0.20:1, for example 0.10 to 0.20:1.

In an embodiment, the composition does not comprise a sulphatecomponent; that is to say that the composition is essentially free fromalkali metal sulphates and alkaline earth metal sulphates; in particularessentially free from sodium sulphate, potassium sulphate and magnesiumsulphate.

Preferred flavouring agents are as set out above in section 3a) inrelation to solutions of the invention. For example the composition maycomprise a flavouring agent in a weight ratio to PEG of 0.0005 to0.050:1, for example 0.001 to 0.025:1, for example 0.0025 to 0.020:1.

Preferred sweeteners are as set out above in section 3a) in relation tosolutions of the invention. For example the composition may comprise asweetener in a weight ratio to PEG of 0.0005 to 0.1:1, for example 0.001to 0.075:1, for example 0.002 to 0.050:1.

In particular, the invention provides a composition comprising thefollowing components in the following weight ratios:

a) ascorbate anion: 0.82 to 4.0 parts

b) PEG having an average molecular weight of 3000 to 4000 Da: 1.0 part.

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents; and

f) optionally one or more sweeteners;

the ascorbate anion being provided by

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0.

Each of c) and d) may be present in the weight ratios to PEG describedabove. Each of e) and f) may be as described above and/or be in theweight ratios to PEG described above.

In one embodiment, the invention provides a composition comprising thefollowing components in the following weight ratios:

a)

-   -   (i) ascorbic acid: 0.12 to 0.30 parts; and    -   (ii) sodium ascorbate: 0.9 to 1.9 parts    -   the components (i) and (ii) being present in a weight ratio of        from 1:5063 to 1:7.875;

b) PEG having an average molecular weight of 3000 to 4000 Da: 1 part

c) sodium chloride 0.05 to 0.10 parts and litre potassium chloride 0.02to 0.04 parts;

e) one or more flavouring agents: 0.001 to 0.075 parts; and

f) one or more sweeteners: 0.002 to 0.050 parts.

For example, the composition may comprise the following components inthe following weight ratios:

a)

-   -   (i) ascorbic acid: 0.189 parts; and    -   (ii) sodium ascorbate: 1.20 parts

b) PEG having an average molecular weight of 3000 to 4000 Da: 1 part

c) sodium chloride 0.08 parts and litre potassium chloride 0.03 parts;

e) one or more flavouring agents: 0.001 to 0.075 parts; and

f) one or more sweeteners: 0.002 to 0.050 parts.

For example, the flavouring and sweetener may be 0.015 parts orangeflavour and 0.048 parts aspartame. For example, the flavouring andsweetener may be 0.040 parts citrus flavour and 0.022 parts aspartame.For example, the flavouring and sweetener may be 0.053 parts orangegrapefruit flavour and 0.022 parts aspartame.

In an embodiment, the composition consists essentially of thosecomponents; that is to say that it does not contain any furthercomponents in significant quantities. The composition may, for example,not contain any sulphate.

Preferred compositions of the invention are dry compositions, forexample dry powder compositions.

In a further aspect, the invention provides a composition comprising thefollowing components in the following weight ratios:

-   -   (i) ascorbic acid: 1 part and    -   (ii) one or more salts of ascorbic acid: 5.063 to 7.875 parts

The salt of ascorbic acid can be sodium ascorbate. A mixture of ascorbicacid and sodium ascorbate in a molar ratio of from 1:4.5 to 1:7.0 hasascorbic acid and sodium ascorbate present in a weight ratio of 1:5.063to 1:7.875. A more preferred ratio is 1:5.344 to 1:7.594; morepreferably from 1:5.625 to 1:6.75; for example from 1:6.075 to 1:6.525,for example 1:6.38.

f) Methods of Preparing Solutions and Compositions

The invention further provides a method of preparing a solution of theinvention comprising combining the components of the solution withwater. The method comprises the step of combining the components withwater and admixing. Some or all of the components may be in physicalassociation with each other before the water is added. In someembodiments, the components of the composition are provided in more thanone part; that is to say that they are packaged separately. All of thecomponents may be combined with each other before combining with water.For example, if flavouring agent and sweetener are packaged separatelyfrom other components, they may be combined with the other componentsbefore combining with water. One or some of the components may becombined with water and admixed in a first step and then some or all ofthe remaining components may be added in a second step. For example, thecomponents may be in dry form, for example in powder form.

As set out above in section 3d), the invention provides a composition(for example a dry composition, for example a powder) for thepreparation of a solution of the invention. The invention furtherprovides a method of preparing a composition of the invention comprisingcombining the components of the composition. For example, the method maybe a method of preparing a composition of the invention in powder form.As set out in section 3d) above, the components for the preparation of asolution of the invention may be presented in two or more parts. Theinvention thus further provides a method of preparing a composition ofthe invention comprising combining some, but not all of the componentsof the composition. The invention thus provides a method comprisingblending a mixture of:

-   -   (i) ascorbic acid: 1 part and    -   (ii) one or more salts of ascorbic acid: 5.063 to 7.875 parts

The salt of ascorbic acid can be sodium ascorbate. A mixture of ascorbicacid and sodium ascorbate in a molar ratio of from 1:4.5 to 1:7.0 hasascorbic acid and sodium ascorbate present in a weight ratio of 1:5.063to 1:7.875. A more preferred ratio is 1:5.344 to 1:7.594; morepreferably from 1:5.625 to 1:6.75; for example from 1:6.075 to 1:6.525,for example 1:6.38.

The method may comprise blending a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0.

Preferred salts of ascorbic acid are as set out above in section 3a).Preferred ratios of components (i) and (ii) are as set out above insection 3a).

The method may further comprise blending a mixture of:

a) ascorbate anion: 0.82 to 4.0 parts;

b) polyethylene glycol: 1.0 part;

c1) sodium chloride: 0.005 to 1.0 parts; and

c2) potassium chloride: 0.005 to 1.0 parts;

the ascorbate anion being provided by

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0.

The components may be weighed out and added together before blending, orthe components may be added into a blend mixture in any desired order.

Blending of the compositions in bulk may, for example, be carried out ona 100 Kg, 500 Kg or 1000 Kg scale. After blending, the composition isdivided into smaller portions for packaging into dosage amounts. Theinvention thus provides a method comprising the step of dividing bulkcomposition as set out in section 3e) above into smaller portions. Theinvention also provides a method comprising the step of fillingcontainers with individual dosage amounts of bulk composition as set outin section 3e). The invention thus provides a method comprising the stepof filling a container with a composition as set out in section 3d). Thecomposition as set out in section 3d) may be presented in two or moreparts. The method may thus comprise the step of filling a container withsome but not all of the components of a composition as set out insection 3d).

4. ALTERNATIVE SOLUTIONS

The invention also provides a colon cleansing solution does not containany ascorbic acid. The invention thus provides, in a second aspect, acolon cleansing solution comprising:

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid

b) 10 to 200 g per litre polyethylene glycol;

the solution being essentially free from ascorbic acid.

The solution of the invention has advantageous properties. The solutionof the invention has a surprisingly palatable taste and it is highlyeffective as a colon cleansing solution with a good tolerabilityprofile.

5. DETAILED DESCRIPTION

a) Contents of Solutions

The solutions of the invention are aqueous solutions. Suitable salts ofascorbic acid include alkali metal salts and alkaline earth metal salts.For example a salt may be selected from sodium, potassium, magnesium andcalcium salts. For example, preferred salts of ascorbic acid includesodium ascorbate, potassium ascorbate, magnesium ascorbate and calciumascorbate. Particularly preferred salts of ascorbic acid are magnesiumascorbate and sodium ascorbate, for example sodium ascorbate. In oneembodiment, the solution comprises sodium ascorbate and no furtherascorbate.

The solution of the invention preferably comprises ascorbate anion in aconcentration of: 370-430 mmol per litre, for example 380-420 mmol perlitre, for example 400-410 mmol per litre.

A solution of the invention may comprise 72 to 88 g/litre of ascorbatesalt. For example, a solution of the invention comprises 75 to 85g/litre, for example 78 to 82 g/litre, for example 80 g/litre.

Sodium ascorbate has a molecular weight of 198 g/mol. Accordingly, asolution of the invention may comprise sodium ascorbate at 71.3-87.1 gper litre, for example 73.3-85.1 g per litre for example 75.2-83.2 g perlitre, for example 79.2-80.2 g per litre.

Potassium ascorbate has a molecular weight of 214 g/mol. Accordingly, asolution of the invention may comprise potassium ascorbate at 77.0-94.2g per litre, 79.2-92.0 g per litre, for example 81.3-89.9 g per litre,for example 85.6-86.7 g per litre.

Magnesium ascorbate has a molecular weight of 374.5 g/mol and each moleof magnesium ascorbate provides two moles of ascorbate. Accordingly, asolution of the invention may comprise magnesium ascorbate at 67.4-82.4g per litre, for example 69.3-80.5 g per litre, for example 71.2-78.6 gper litre, for example 74.9-75.8 g per litre

Depending on the pH of the solution, some ascorbate anion may beprotonated and thus exist as free ascorbic acid in solution. At the pHof solutions that would typically be administered, only a minorproportion of ascorbate is protonated. In calculations of concentrationsof “ascorbate anion” herein, the concentration of “ascorbate anion” istaken as the total concentration of all ascorbate anion present,including the proportion that is protonated.

The cleansing solution comprises polyethylene glycol. The polyethyleneglycol (PEG) may be as described above in section 3a). The cleansingsolution comprises 10 to 200 g per litre of PEG. Preferably, thesolution comprises 20 to 160 g per litre of PEG, more preferably 40 to120 g per litre, for example 60 to 100 g per litre, for example 75 to 85g per litre, for example 80 g per litre.

The cleansing solution may additionally comprise one or more of:

c) one or more electrolytes;

d) one or more alkali metal or alkaline earth metal sulphates;

e) one or more flavouring agents;

f) one or more sweeteners.

The cleansing solution may comprise one or more electrolytes.Electrolytes include salts of sodium, potassium, calcium and magnesium,particularly sodium and potassium; and salts of chloride, iodide,bicarbonate and carbonate, particularly chloride. Preferred electrolytesare sodium chloride and potassium chloride. In an embodiment, thesolution is essentially free from sodium bicarbonate, for exampleessentially free from any bicarbonate.

For example, the solution may comprise sodium chloride at aconcentration of 1 to 10 g per litre. For example, sodium chloride maybe present at a concentration of 3 to 8 g per litre, for example 4 to 7g per litre; for example 4.5 to 5.5 g per litre; for example 5.0 g perlitre or 5.6 g per litre.

For example, the solution may comprise potassium chloride at aconcentration of 1 to 10 g per litre. For example, potassium chloridemay be present at a concentration of 1 to 7 g per litre, for example 1.5to 5 g per litre, for example 1.5 to 3 g per litre, for example 1.7 to2.8 g per litre; for example 1.8 g per litre or 2.6 g per litre.

In an embodiment, the solution comprises sodium chloride and potassiumchloride. They can be present in the amounts mentioned immediatelyabove. For example, sodium chloride may be present at a concentration of4 to 7 g per litre and potassium chloride may be present at aconcentration of 1.5 to 3 g per litre.

The cleansing solution may comprise one or more alkali metal sulphates,alkaline earth metal sulphates or a mixture thereof (herein referred toas a “sulphate component”). The sulphate component and the quantitythereof may be as described above in section 3a).

In an alternative preferred embodiment, the solution does not comprise asulphate component; that is to say that the solution is essentially freefrom alkali metal sulphates and alkaline earth metal sulphates; inparticular essentially free from sodium sulphate, potassium sulphate andmagnesium sulphate.

In the solutions of the invention described herein, the quantities ofthe individual components recited do not include any solutes that may bepresent in the water used to prepare the solutions, for example, in hardwater areas there may be significant amounts of Ca²⁺ and Mg²⁺carbonates, bicarbonates or sulphates present in tap water.

The cleansing solution preferably includes a flavouring agent. Theflavouring may be as described above in section 3a). Lemon/lime flavourand orange flavour are particularly preferred.

The amount of flavouring required depends on the nature and strength ofthe flavouring in question. Typically, it is 0.05 to 4.5 g per litre,for example 0.05 to 2.0 g per litre, for example 0.5 to 1.8 g per litre,for example 2.5 to 4.5 g per litre, for example 0.6 g per litre or 1.6 gper litre, for example 3.2 or 4.3 g per litre.

The cleansing solution preferably includes a sweetener. The sweetenermay be as described above in section 3a).

Alternatively, compositions of the invention can be essentially freefrom added sweeteners, for example to minimize the number of differentcomponents in the compositions.

A souring agent (for example citric acid) may be present as a tasteenhancer. A souring agent is a component that imparts a sourness to acomposition. Other souring agents include malic acid, acetic acid,tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid,phytic acid, lactic acid or salts thereof. The souring agent (forexample citric acid) may be provided in an encapsulated form. Theencapsulation provides a coating that isolates the souring agent fromother components and from air and moisture prior to its use. Severalencapsulated forms of citric acid, or other souring agents, arecommercially available. For example, the encapsulation may be with awater-soluble coating.

The amount of sweetener required depends on the nature and strength ofthe sweetener being considered. Typically, it is 0.10 to 4 g per litre.For example, the sweetener may be aspartame at 0.5 to 4 g per litre, forexample 2.5 to 4.0 g per litre, for example 2.0 g per litre, for example2.2 g per litre or 3.25 g per litre. Those quantities of aspartame areparticularly suitable when used with orange flavouring, for exampleorange flavouring at 0.2 to 1.8 g per litre, for example 0.5 to 1.8 gper litre, for example 0.6 g per litre or 1.6 g per litre or 3.25 g perlitre.

The invention thus provides a colon cleansing solution comprising:

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid;

b) 10 to 200 g per litre PEG;

c) one or more electrolytes;

d) optionally one or more alkali metal or alkaline earth metalsulphates;

e) optionally one or more flavouring agents; and

f) optionally one or more sweeteners;

the solution being essentially free from ascorbic acid.

In particular, the invention provides a colon cleansing solutioncomprising:

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid;

b) 10 to 200 g per litre PEG having an average molecular weight of 3000to 4000 Da;

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents; and

f) optionally one or more sweeteners;

the solution being essentially free from ascorbic acid.

Each of c) and d) may be present in the concentrations described above.Each of e) and f) may be as described above and/or be in theconcentrations described above.

In particular, the invention provides a colon cleansing solutioncomprising:

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid;

b) 10 to 200 g per litre PEG having an average molecular weight of 3000to 4000 Da;

c) sodium chloride and potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners;

the solution being essentially free from ascorbic acid.

In one embodiment, the one or more components of c), d) (when present),e) and f) are present in the solution. In an alternative presentation,some or all of components c), d) (when present), e) and f) may beprovided separately from the solution, for example in a tablet orcapsule. In an embodiment, the solution may comprise a) the ascorbatecomponent and b) PEG, and optional flavouring and sweetener (e) and f)),and a tablet or capsule may comprise c) the one or more electrolytesand/or d) the one or more alkali metal or alkaline earth metalsulphates, again with optional flavouring and sweetener (e) and f)). Theflavouring and sweeteners need not be the same in the tablet or capsuleas in the solution.

In one embodiment, the invention provides a colon cleansing solutioncomprising:

a) 71.3 to 87.1 g per litre sodium ascorbate

b) 60 to 100 g per litre PEG having an average molecular weight of 3000to 4000 Da;

c) 3 to 8 g per litre sodium chloride and 1 to 7 g per litre potassiumchloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

In an embodiment, the solution consists essentially of those components;that is to say that it does not contain any further components insignificant quantities. The solution may, for example, not contain anysulphate.

In particular, the invention provides a solution consisting essentiallyof:

a) 75 to 85 g per litre sodium ascorbate

b) 75 to 85 per litre PEG having an average molecular weight of 3000 to4000 Da;

c) 4.5 to 5.5 g per litre sodium chloride and 1.5 to 2.3 g per litrepotassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

For example, the invention provides a colon cleansing solutionconsisting essentially of:

a) 80 g per litre sodium ascorbate

b) 80 g per litre PEG having an average molecular weight of 3000 to 4000Da;

c) 5.0 g per litre sodium chloride and 1.80 g per litre potassiumchloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

For example, the flavouring and sweetener may be 1.60 g per litre orangeflavour and 2.20 g per litre aspartame. For example, the flavouring andsweetener may be 3.20 g per litre lemon/lime flavour and 3.25 g perlitre aspartame. For example, the flavouring and sweetener may be 4.30 gper litre orange grapefruit flavour and 3.25 g per litre aspartame.

Preferably, the colon cleansing solution is hyper-osmotic. That is tosay that it has a higher osmotic strength than blood in the human body.It may, for example have a measured osmolality in the range 500 to 2000mOsmol/kg. For example, the osmolality may be in the range 700 to 1800mOsmol/kg. For example, the solutes in 500 ml of the solution may have ameasured V(350) value of from 1000 to 2000 ml, for example from 1300 to1700 ml, for example from 1400 to 1600 ml, and be in a volume of 400 to600 ml, for example 500 ml.

The invention provides a colon cleansing solution comprising:

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid

b) 10 to 200 g per litre polyethylene glycol;

the solution being essentially free from ascorbic acid, and 500 ml ofthe solution having a V(350) osmolality value of from 1000 to 2000 ml.

For example, 500 ml of the solution may have a V(350) osmolality valueof from 1200 to 1800 ml, for example from 1400 to 1600 ml.

b) Additional Optional Contents of Solutions

The solutions of the invention may include additional optionalcomponents as set out above in section 3b).

c) Uses of Solutions of the Invention

Uses of solutions of the invention are as set out above in section 3c).The invention thus provides, in a further aspect a solution in water of:

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid; and

b) optionally 10 to 200 g per litre polyethylene glycol,

the solution being essentially free from ascorbic acid,

for use in cleansing the colon of a mammal.

The solution for use in cleansing the colon of a mammal preferablycomprises ascorbate anion in a concentration of: 370-430 mmol per litre,for example 380-420 mmol per litre, for example 400-410 mmol per litre.As set out above, the ascorbate anion is provided by one or more saltsof ascorbic acid. Preferred forms of the ascorbate component are as setout above in section 5a).

In a preferred embodiment, PEG is present. Preferred forms of the PEGand preferred amounts thereof are as set out above in section 5a).

The solution for use in cleansing the colon of a mammal may additionallycomprise one or more of:

c) one or more electrolytes;

d) one or more alkali metal or alkaline earth metal sulphates;

e) one or more flavouring agents;

f) one or more sweeteners.

For example, the solution for use in cleansing the colon of a mammaladditionally comprises elements c), e) and f) from that list.

Preferred electrolytes and preferred amounts thereof are as set outabove in section 5a).

Preferred alkali metal or alkaline earth metal sulphates and preferredamounts thereof are as set out above in section 5a).

Preferred flavouring agents and preferred amounts thereof are as set outabove in section 5a).

Preferred sweeteners and preferred amounts thereof are as set out abovein section 5a).

For example, the solution in water comprises:

a) 180 to 220 mmol ascorbate anion provided by one or more salts ofascorbic acid; and

b) optionally 5 to 100 g PEG.

the solution being essentially free from ascorbic acid.

In particular, the invention provides a solution comprising:

a) 180 to 220 mmol ascorbate anion provided by one or more salts ofascorbic acid;

b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da;

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents; and

f) optionally one or more sweeteners,

the solution being essentially free from ascorbic acid

for use in cleansing the colon of a mammal.

Each of c) and d) may be as described above and/or be present in theamounts described above in relation to solutions of the invention. Eachof e) and f) may be as described above and/or be in the amountsdescribed above in section 5a).

In particular, the invention provides a solution consisting essentiallyof:

a) 75 to 85 g per litre sodium ascorbate

b) 75 to 85 per litre PEG having an average molecular weight of 3000 to4000 Da;

c) 4.5 to 5.5 g per litre sodium chloride and 1.5 to 2.3 g per litrepotassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners,

for use in cleansing the colon of a mammal.

For example, the invention provides a solution consisting essentiallyof:

a) 80 g per litre sodium ascorbate

b) 80 g per litre PEG having an average molecular weight of 3000 to 4000Da;

c) 5.0 g per litre sodium chloride and 1.80 g per litre potassiumchloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

for use in cleansing the colon of a mammal.

For example, the flavouring and sweetener may be 1.60 g per litre orangeflavour and 2.20 g per litre aspartame. For example, the flavouring andsweetener may be 3.20 g per litre lemon/lime flavour and 3.25 g perlitre aspartame. For example, the flavouring and sweetener may be 4.30 gper litre orange grapefruit flavour and 3.25 g per litre aspartame.

As mentioned above, a bowel cleansing treatment typically involves asubject taking a single dose or a split dose of cleansing solution. Thevolume of solution that a subject takes in a single dose treatment isdescribed hereinabove in section 3c). The subject may take someadditional clear fluid after taking the solution as describedhereinabove.

The volume of solution that a subject takes in a split dose treatment isdescribed hereinabove in section 3c). The subject may take someadditional clear fluid after each or either dose the solution asdescribed hereinabove.

d) Compositions for Preparing Doses of Solutions

The invention further provides a composition (for example a drycomposition, for example a powder) for the preparation of a solution ofthe invention. A composition can be provided in a quantity for thepreparation of a dose of the solution, for example a 500 ml dose. Theinvention provides a composition for admixture with water, wherein thecomposition is optionally presented in two or more parts and comprises:

a) 180 to 220 mmol ascorbate anion provided by one or more salts ofascorbic acid; and

b) 5 to 100 g polyethylene glycol;

the solution being essentially free from ascorbic acid.

For example, the components may be in dry powder, granular or other dryform. They may alternatively be in the form of concentrates or slurries.Components may be in the same or different physical forms. For example,the composition is a dry composition, for example a dry powdercomposition. For example, one or both of components a) and b) are drypowders.

As set out above in section 5a), the ascorbate anion may be provided byone or more salts of ascorbic acid. Preferred forms of the ascorbatecomponent are as set out above in relation to solutions of theinvention.

The composition of the invention preferably comprises ascorbate anion inan amount of: 185 to 215 mmol, for example 190 to 210 mmol, for example200-205 mmol

Sodium ascorbate has a molecular weight of 198 g/mol. Accordingly, the180 to 220 mmol ascorbate anion can be provided by 35.6 to 43.6 g sodiumascorbate. For example, the sodium ascorbate may be present at a levelof 36.6 to 42.6 g, for example 37.6 to 41.6 g, for example 39.6 to 40.6g.

Potassium ascorbate has a molecular weight of 214 g/mol. Accordingly,the 180 to 220 mmol ascorbate anion can be provided by 38.5 to 47.1 gpotassium ascorbate. For example, the potassium ascorbate may be presentat a level of 39.6 to 46.0 g, for example 40.7 to 44.9 g, for example42.8 to 43.9 g.

Magnesium ascorbate has a molecular weight of 374.5 g/mol and each moleof magnesium ascorbate provides two moles of ascorbate. Accordingly, the180 to 220 mmol ascorbate anion can be provided by 33.7 to 41.2 gmagnesium ascorbate. For example, the magnesium ascorbate may be presentat a level of 34.6 to 40.3 g, for example 35.6 to 39.3 g, for example37.5 to 38.4 g.

The weight of the ascorbate salt component may be 33 to 47 g, forexample 35 to 45 g, for example 37 to 43 g.

In an embodiment, the ascorbate component consists essentially of sodiumascorbate alone. For example, it may be present in an amount asmentioned immediately above.

Preferred forms of the PEG are as set out in section 5a) above inrelation to solutions of the invention. The composition comprises 5 to100 g of PEG. Preferably, the composition comprises 10 to 80 g of

PEG, more preferably 20 to 60 g, for example 30 to 50 g, for example37.5 to 42.5 g, for example 40 g of PEG.

The composition may additionally comprise one or more of:

c) one or more electrolytes;

d) one or more alkali metal or alkaline earth metal sulphates;

e) one or more flavouring agents; and

f) one or more sweeteners.

Preferred electrolytes are as set out above in section 5a) in relationto solutions of the invention. For example, the composition may comprisesodium chloride in an amount of 0.5 to 5 g, for example 1.5 to 4 g, forexample 2.0 to 3.5 g, for example 2.5 or 2.8 g. For example, thecomposition may comprise potassium chloride in an amount of 0.5 to 5 g,for example 0.5 to 3.5 g, for example 0.75 to 2.5 g, for example 0.75 to1.5 g, for example 0.85 to 1.4 g, for example 0.9 or 1.3 g. In anembodiment, the composition is essentially free from sodium bicarbonate,for example essentially free from any bicarbonate.

Preferred alkali metal or alkaline earth metal sulphates are as set outabove in relation to solutions of the invention. For example, thecomposition may comprise a sulphate component in an amount of 1 to 10 g,for example 2.5 to 7.5 g, for example 4 to 7.5 g, for example 5 to 7 g,for example 6 g. The one or more sulphate salts may be provided in anypharmaceutically acceptable form: they may each be anhydrous, or be in ahydrated form. The weights mentioned herein refer to the weight of thesulphate salt excluding any water of hydration. A hydrate form may bepresent in the dry powder composition, and that composition is stillconsidered “dry” herein. In an alternative preferred embodiment, thecomposition does not comprise a sulphate component; that is to say thatthe solution is essentially free from alkali metal sulphates andalkaline earth metal sulphates; in particular essentially free fromsodium sulphate, potassium sulphate and magnesium sulphate.

Preferred flavouring agents are as set out above in section 5a) inrelation to solutions of the invention. For example the amount offlavouring agent may be 0.025 to 2.25 g, for example 0.025 to 1.0 g, forexample 0.25 to 0.9 g, for example 1.25 to 2.25 g, for example 0.3 g or0.8 g, for example 1.6 or 2.15 g.

Preferred sweeteners are as set out above in relation to solutions ofthe invention. For example the amount of sweetener may be 0.05 to 2 g.For example, the sweetener may be aspartame at 0.25 to 2 g, for exampleat 1.25 to 2.0 g, for example 1.0, 1.1 g or 1.625 g. Those quantities ofaspartame are particularly suitable when used with orange flavouring,for example orange flavouring at 0.1 to 0.9 g, for example 0.25 to 0.9g, for example 0.3, 0.8 g or 1.625 g.

In particular, the invention provides a composition comprising:

a) 180 to 220 mmol ascorbate anion provided by one or more salts ofascorbic acid;

b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da.

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents;

f) optionally one or more sweeteners;

the solution being essentially free from ascorbic acid.

Each of c) and d) may be present in the amounts described above. Each ofe) and f) may be as described above and/or be in the amounts describedabove.

In one embodiment, the invention provides composition comprising:

a) 35.65 to 43.55 g sodium ascorbate

b) 30 to 50 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 1.5 to 4 g sodium chloride and 0.5 to 3.5 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

In one embodiment, the invention provides a composition comprising:

a) 40 g sodium ascorbate

b) 40 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 2.50 g sodium chloride and 0.90 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

For example, the flavouring and sweetener may be 0.80 g orange flavourand 1.10 g aspartame. For example, the flavouring and sweetener may be1.60 g lemon/lime flavour and 1.625 g aspartame. For example, theflavouring and sweetener may be 2.15 g orange grapefruit flavour and1.625 g aspartame.

In an embodiment, the composition consists essentially of thosecomponents; that is to say that it does not contain any furthercomponents in significant quantities. The composition may, for example,not contain any sulphate.

One or more components a) to f) may be presented in solid form, or insemi-solid form (for example in gel form).

In one embodiment, the one or more components of c), d) e) and f) arepresent in the composition for making up a solution. In an alternativepresentation, some or all of components c), d) e) and f) may be providedseparately from the composition for making up the solution, for examplein a tablet or capsule. In an embodiment, there may be provided theascorbate component and PEG, and optional flavouring and sweetener, in aform for admixture with water, and a tablet or capsule comprising theone or more electrolytes and/or the one or more alkali metal or alkalineearth metal sulphates, again with optional flavouring and sweetener. Theflavouring and sweeteners need not be the same in the tablet or capsuleas in the composition for admixture with water.

In some embodiments, it is desirable to package the ascorbate and thePEG components separately from each other.

In an embodiment, the composition can be provided to the subject with aplurality of flavouring agents (each optionally with one or moresweeteners), each separately packaged. The subject can then select apreferred flavouring (or flavouring and sweetener combination) accordingto his or her taste. The subject also has the choice of not using anyflavouring or sweetener at all.

It will be apparent to the reader that all compounds and compositionsdescribed herein are of a nature and quality suitable for mammalian(especially human) consumption. For example, they are of pharmaceuticalgrade. The pharmaceutically acceptable compositions described herein maybe provided in packaged form with instructions for use.

e) Compositions for Preparing Solutions

In a further aspect, the invention provides a composition comprising thefollowing components in the following weight ratios:

a) ascorbate anion 0.78 to 1.2 parts; and

b) polyethylene glycol 1.0 part;

the ascorbate anion being provided by one or more salts of ascorbicacid;

the composition being essentially free from ascorbic acid.

As mentioned above, for example, the components may be in dry powder,granular or other dry form.

They may alternatively be in the form of concentrates or slurries.Components may be in the same or different physical forms. For example,the composition is a dry composition, for example a dry powdercomposition. For example, one or both of components a) and b) are drypowders.

As set out above, the ascorbate anion is provided by one or more saltsof ascorbic acid. Preferred forms of the ascorbate component are as setout above in section 5a) in relation to solutions of the invention.Preferred salts are sodium, potassium and magnesium ascorbate,especially sodium ascorbate.

Preferred forms of the PEG are as set out above in section 5a) inrelation to solutions of the invention. The composition of the inventionpreferably comprises ascorbate anion in a weight ratio to PEG of 0.80 to1.0:1. More preferably, the weight ratio is 0.85 to 0.95:1, for example0.86 to 0.90:1, for example 0.88:1.

The preferred ascorbate salt is sodium ascorbate. The composition of theinvention preferably comprises sodium ascorbate and PEG in a weightratio of 0.90 to 1.125:1. More preferably, the weight ratio is 0.956 to1.069:1, for example 0.968 to 1.013:1, for example 0.99:1, for example1:1.

The composition may additionally comprise one or more of:

c) one or more electrolytes;

d) one or more alkali metal or alkaline earth metal sulphates;

e) one or more flavouring agents;

f) one or more sweeteners.

Preferred electrolytes are as set out above in section 5a) in relationto solutions of the invention. For example, the composition may comprisesodium chloride in a weight ratio to PEG of 0.005 to 0.5:1, for example0.01 to 0.3:1, for example 0.02 to 0.2:1, for example 0.03 to 0.15:1,for example 0.04 to 0.1:1, for example 0.05 to 0.08:1. For example, thecomposition may comprise potassium chloride in a weight ratio to PEG of0.005 to 0.30:1, for example 0.01 to 0.20:1, for example 0.01 to 0.10:1,for example 0.02 to 0.04:1.

For example, the invention provides a composition comprising thefollowing components in the following weight ratios:

a) ascorbate anion: 0.78 to 1.2 parts;

b) polyethylene glycol: 1.0 part;

c1) sodium chloride: 0.005 to 1.0 parts; and

c2) potassium chloride: 0.005 to 1.0 parts;

the ascorbate anion being provided by one or more salts of ascorbicacid;

the composition being essentially free from ascorbic acid.

The composition is preferably essentially free from sodium bicarbonate.For example, it is essentially free from any bicarbonate.

Preferred alkali metal or alkaline earth metal sulphates are as set outabove in section 5a) in relation to solutions of the invention. Forexample, the composition may comprise a sulphate component (for examplesodium sulphate) in a weight ratio to PEG of 0.01 to 0.50:1, Forexample, the composition may comprise a sulphate component (for examplesodium sulphate) in a weight ratio to PEG of 0.02 to 0.25:1, for example0.03 to 0.22:1, for example 0.05 to 0.20:1, for example 0.10 to 0.20:1.

In an alternative preferred embodiment, the composition does notcomprise a sulphate component; that is to say that the composition isessentially free from alkali metal sulphates and alkaline earth metalsulphates; in particular essentially free from sodium sulphate,potassium sulphate and magnesium sulphate.

Preferred flavouring agents are as set out above in section 5a) inrelation to solutions of the invention. For example the composition maycomprise a flavouring agent in a weight ratio to PEG of 0.0005 to0.05:1, for example 0.001 to 0.050:1, for example 0.003 to 0.030:1.

Preferred sweeteners are as set out above in section 5a) in relation tosolutions of the invention. For example the composition may comprise asweetener in a weight ratio to PEG of 0.0005 to 0.025:1, for example0.001 to 0.050:1, for example 0.01 to 0.035:1.

In particular, the invention provides a composition comprising thefollowing components in the following weight ratios:

a) ascorbate anion: 0.78 to 1.2 parts

b) PEG having an average molecular weight of 3000 to 4000 Da: 1.0 part.

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents; and

f) optionally one or more sweeteners.

the ascorbate anion being provided by one or more salts of ascorbicacid;

the composition being essentially free from ascorbic acid.

Each of c) and d) may be present in the weight ratios to PEG describedabove. Each of e) and f) may be as described above and/or be in theweight ratios to PEG described above.

In one embodiment, the invention provides a composition comprising thefollowing components in the following weight ratios:

a) sodium ascorbate: 0.90 to 1.125 parts

b) PEG having an average molecular weight of 3000 to 4000 Da: 1 part

c) sodium chloride 0.04 to 0.10 parts and litre potassium chloride 0.02to 0.04 parts;

e) one or more flavouring agents: 0.001 to 0.075 parts; and

f) one or more sweeteners: 0.002 to 0.050 parts.

For example, the composition may comprise the following components inthe following weight ratios:

a) sodium ascorbate: 1.0 parts

b) PEG having an average molecular weight of 3000 to 4000 Da: 1 part

c) sodium chloride 0.0625 parts and litre potassium chloride 0.0225parts;

e) one or more flavouring agents: 0.001 to 0.075 parts; and

f) one or more sweeteners: 0.002 to 0.050 parts.

For example, the flavouring and sweetener may be 0.020 parts orangeflavour and 0.0275 parts aspartame. For example, the flavouring andsweetener may be 0.040 parts lemon/lime flavour and 0.041 partsaspartame. For example, the flavouring and sweetener may be 0.054 partsorange flavour and 0.041 parts aspartame.

In an embodiment, the composition consists essentially of thosecomponents; that is to say that it does not contain any furthercomponents in significant quantities. The composition may, for example,not contain any sulphate.

Preferred compositions of the invention are dry compositions, forexample dry powder compositions.

f) Methods of Preparing Solutions and Compositions

The invention further provides a method of preparing a solution of theinvention comprising combining the components of the solution withwater. The method comprises the step of combining the components withwater and admixing. Some or all of the components may be in physicalassociation with each other before the water is added. In someembodiments, the components of the composition are provided in more thanone part; that is to say that they are packaged separately. All of thecomponents may be combined with each other before combining with water.For example, if flavouring agent and sweetener are packaged separatelyfrom other components, they may be combined with the other componentsbefore combining with water. One or some of the components may becombined with water and admixed in a first step and then or all of theremaining components may be added in a second step. For example, thecomponents may be in dry form, for example in powder form.

As set out above in section 5d), the invention provides a composition(for example a dry composition, for example a powder) for thepreparation of a solution of the invention. The invention furtherprovides a method of preparing a composition of the invention comprisingcombining the components of the composition. For example, the method maybe a method of preparing a composition of the invention in powder form.The method may comprise blending a mixture of:

a) ascorbate anion 0.78 to 1.2 parts; and

b) polyethylene glycol 1.0 part;

the ascorbate anion being provided by one or more salts of ascorbicacid;

the composition being essentially free from ascorbic acid

Preferred ascorbate salts are as set out above in section 5a). Preferredratios of components a) and b) as as set out above in section 5a).Preferably the ascorbate anion is in a weight ratio to PEG of 0.80 to1.0:1. More preferably, the weight ratio is 0.85 to 0.95:1, for example0.86 to 0.90:1, for example 0.88:1.

The preferred ascorbate salt is sodium ascorbate. Preferably the sodiumascorbate and PEG are in a weight ratio of 0.90 to 1.125:1. Morepreferably, the weight ratio is 0.956 to 1.069:1, for example 0.968 to1.013:1, for example 0.99:1, for example 1:1.

The method may further comprise blending a mixture of:

a) ascorbate anion: 0.78 to 1.2 parts;

b) polyethylene glycol: 1.0 part;

c1) sodium chloride: 0.005 to 1.0 parts; and

c2) potassium chloride: 0.005 to 1.0 parts;

the ascorbate anion being provided by one or more salts of ascorbicacid;

the composition being essentially free from ascorbic acid.

Preferred ratio amounts of sodium chloride to PEG and potassium chlorideto PEG are as set out above in section 5e).

The components may be weighed out and added together before blending, orthe components may be added into a blend mixture in any desired order.

Blending of the compositions in bulk may, for example, be carried out ona tonne scale. After blending, the composition is divided into smallerportions for packaging into dosage amounts. The invention thus providesa method comprising the step of dividing bulk composition as set out insection 5e) above into smaller portions. The invention also provides amethod comprising the step of filling containers with individual dosageamounts of bulk composition as set out in section 5e). The inventionthus provides a method comprising the step of filling a container with acomposition as set out in section 5d). The composition as set out insection 5d) may be presented in two or more parts. The method may thuscomprise the step of filling a container with some but not all of thecomponents of a composition as set out in section 5d).

6. METHODS OF CLEANSING AND SOLUTIONS FOR USE IN THEM

a) Split-Dose Colon Cleansing Treatments

The solutions and compositions of the first and second aspects of theinvention set out in sections 2 to 5 above find particular use in splitdose colon cleansing treatments in which the subject takes two differentagents (for example two different solutions): a first colon cleansingagent (for example solution), followed by a second colon cleansing agent(for example solution). Herein, the “second colon cleansing agent” meansthe agent that is taken chronologically second, after the “first coloncleansing agent”. Preferably, the solution of the first or second aspectof the invention is the second colon cleansing agent. Alternatively, itmay be the first agent. The invention thus provides, in a third aspect amethod of cleansing the colon of a mammal comprising:

-   -   the subject taking an effective amount of a first colon        cleansing agent; and then    -   the subject taking an effective amount of a second colon        cleansing agent,        the second colon cleansing agent being a solution of the first        or second aspect of the invention described above. Preferably,        the first colon cleansing agent is of different composition from        the second colon cleansing agent. The first colon cleansing        agent may be a colon cleansing solution. Alternatively, it may        be a colon cleansing agent in solid form, for example in the        form of a tablet, for example a PEG-containing tablet, or a        bisacodyl-containing tablet. The first colon cleansing agent        may, for example, contain a laxative, for example a stimulant        laxative. For example, bisacodyl, castor oil, senna or bisoxatin        may be used.

The invention also provides a method of cleansing the colon of a mammalcomprising:

-   -   the subject taking an effective amount of a first colon        cleansing agent; and then    -   the subject taking an effective amount of a second colon        cleansing agent,

the second colon cleansing agent being a solution comprising

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid        the components (i) and (ii) being present in a molar ratio of        from 1:4.5 to 1:7.0; and

b) optionally 10 to 200 g per litre polyethylene glycol.

The invention also provides a method of cleansing the colon of a mammalcomprising:

-   -   the subject taking an effective amount of a first colon        cleansing agent; and then    -   the subject taking an effective amount of a second colon        cleansing agent, the second colon cleansing agent being a        solution comprising

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid; and

b) optionally 10 to 200 g per litre polyethylene glycol;

the solution being essentially free from ascorbic acid.

The method of the invention may be used to cleanse the colon prior tocarrying out a diagnostic, therapeutic or surgical procedure on thecolon, rectum or anus or elsewhere in the abdomen. The diagnostic orsurgical procedure may, for example, be colonoscopy, barium enemaexamination, sigmoidoscopy or colon surgery. The method of the inventionis generally finished less than 8 hours before carrying out thediagnostic, therapeutic or surgical procedure on the colon, rectum oranus or elsewhere in the abdomen. Preferably, it is finished less than 4hours before.

The invention further provides a method of conducting a diagnostic orsurgical procedure, for example, a colonoscopy, barium enemaexamination, sigmoidoscopy or colon surgery, comprising the steps of:

a) cleansing the colon by a method of the invention, and then

b) carrying out the diagnostic or surgical procedure.

The invention further provides a first colon cleansing agent, and asecond colon cleansing agent, for use in a method of cleansing the coloncomprising:

-   -   the subject taking an effective amount of a first colon        cleansing agent;    -   the subject taking an effective amount of a second colon        cleansing agent,        the second colon cleansing agent being a solution of the first        or second aspect of the invention described above.

The invention further provides a first colon cleansing agent, and asecond colon cleansing agent, for use in a method of cleansing the coloncomprising:

-   -   the subject taking an effective amount of a first colon        cleansing agent;    -   the subject taking an effective amount of a second colon        cleansing agent,

the second colon cleansing agent being a solution in water of:

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) optionally 10 to 200 g per litre polyethylene glycol.

In an embodiment, the first agent is different from the second.

The invention further provides a first colon cleansing agent, and asecond colon cleansing agent, for use in a method of cleansing the coloncomprising:

-   -   the subject taking an effective amount of a first colon        cleansing agent;    -   the subject taking an effective amount of a second colon        cleansing agent, the second colon cleansing agent being a        solution in water of:

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid; and

b) optionally 10 to 200 g per litre polyethylene glycol.

the solution being essentially free from ascorbic acid.

In an embodiment, the first agent is different from the second. Furtherdetails of possible first colon cleansing agents are provided below insection 6b)

The second colon cleansing agent is preferably as described hereinabovein sections 2 to 5 in relation to solutions and uses of the first andsecond aspects of the invention. It is preferably used in a volume asdescribed hereinabove in relation to solutions and uses of the inventionas described hereinabove in sections 2 to 5.

The first and second colon cleansing agents may be provided in a kit.Further details of such kits are provided in section 8) below.

b) The “First” Colon Cleansing Agent

The first cleansing agent may be a solution, referred to as the firstcolon cleansing solution. The first colon cleansing solution may, forexample, be a bowel content suspending agent. The first colon cleansingsolution may comprise polyethylene glycol and/or an alkali metalsulphate, an alkaline earth metal sulphate or a mixture thereof. Thefirst colon cleansing solution may be hyper-osmotic.

Preferably, the first colon cleansing solution comprises polyethyleneglycol (PEG). The polyethylene glycol (PEG) may have an averagemolecular weight of 2000 to 8000, for example 2500 to 4500 Da, forexample 2680 to 4020 Da, for example 3000 to 4000 Da. For example, thePEG may be PEG 3350 or PEG 4000 as defined in national pharmacopeias.PEG8000 may also be used. Further examples of suitable PEGs recognizedin some national pharmacopeias include Macrogols, for example Macrogol3350 or Macrogol 4000.

Preferably, the first colon cleansing solution comprises 70 to 250 g perlitre of PEG. Preferably, the solution comprises 130 to 250 g per litrePEG, for example 90 to 200 g per litre of PEG, more preferably 100 to200 g per litre, for example 120 to 150 g per litre, for example 133.3 gper litre; for example 150 to 250 g per litre, for example 175 to 225 gper litre, for example 200 g per litre.

Preferably, the first colon cleansing solution comprises one or morealkali metal sulphates, alkaline earth metal sulphates or a mixturethereof (herein referred to as a “sulphate component”). An alkali metalor alkaline earth metal sulphate may, for example, be selected fromsodium sulphate, potassium sulphate and magnesium sulphate. The solutionmay comprise more than one of sodium sulphate, potassium sulphate andmagnesium sulphate, for example all three. Preferably, the sulphatecomponent is or includes sodium sulphate.

Preferably, the first colon cleansing solution comprises a sulphatecomponent (for example sodium sulphate) at a concentration of 2 to 20 gper litre, for example 2 to 15 g per litre, for example 5 to 15 g perlitre, for example 8 to 12 g per litre, for example 8 or 12 g per litre;for example 10 to 20 g per litre, for example 15 to 20 g per litre, forexample 17 to 19 g per litre, for example 18 g per litre. For example,the first colon cleansing solution comprises 8.0 to 20 g per litre ofone or more alkali metal sulphates, alkaline earth metal sulphates or amixture thereof.

Accordingly, the first colon cleansing solution may comprise:

(i) 70 to 250 g per litre PEG having an average molecular weight of 2500to 4500 Da.

(ii) 2.0 to 20 g per litre of one or more alkali metal sulphates,alkaline earth metal sulphates or a mixture thereof

(iii) optionally one or more electrolytes;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners.

The first colon cleansing solution may comprise one or moreelectrolytes. Electrolytes include salts of sodium, potassium, calciumand magnesium, particularly sodium and potassium; and salts of chloride,iodide, bicarbonate and carbonate, particularly chloride. Preferredelectrolytes are sodium chloride and potassium chloride. In anembodiment, sodium bicarbonate is not included.

For example, the first colon cleansing solution may comprise sodiumchloride at a concentration of 0.5 to 5.0 g per litre. For example,sodium chloride may be present at a concentration of 1.0 to 4.0 g perlitre, for example 1.0 to 3.0 g per litre, for example 1.5 to 3.0 g perlitre, for example 2.0 to 3.0 g per litre; for example 3.0 to 5.0 g perlitre, for example 3.5 to 4.5 g per litre, for example 4.0 g per litre.

For example, the first colon cleansing solution may comprise potassiumchloride at a concentration of 1 to 10 g per litre. For example,potassium chloride may be present at a concentration of 0.05 to 5.0 gper litre, for example 0.1 to 3.0 g per litre, for example 0.2 to 2.0 gper litre, for example 0.5 to 1.5 g per litre, for example 0.5 to 1.1 gper litre; for example 1.5 to 2.5 g per litre, for example 1.8 to 2.2 gper litre, for example 2.0 g per litre.

In an embodiment, the first colon cleansing solution comprises sodiumchloride and potassium chloride. They can be present in the amountsmentioned immediately above. For example, sodium chloride may be presentat a concentration of 1.0 to 3.0 g per litre and potassium chloride maybe present at a concentration of 2.5 to 3.0 g per litre; for example,sodium chloride may be present at a concentration of 3.0 to 5.0 g perlitre and potassium chloride may be present at a concentration of 0.5 to1.1 g per litre.

In an embodiment, the first colon cleansing solution comprises sodiumchloride and potassium chloride. They can be present in the amountsmentioned immediately above. For example, sodium chloride may be presentat a concentration of 1.5 to 3.0 g per litre and potassium chloride maybe present at a concentration of 0.2 to 2.0 g per litre; for example,sodium chloride may be present at a concentration of 3.0 to 5.0 g perlitre and potassium chloride may be present at a concentration of 1.5 to2.5 g per litre.

For example, the first colon cleansing solution comprises:

(i) 90 to 200 g per litre PEG having an average molecular weight of 2500to 4500 Da.

(ii) 2.0 to 15 g per litre of one or more alkali metal sulphates,alkaline earth metal sulphates or a mixture thereof

(iii) 0.5 to 5.0 g per litre sodium chloride, and 0.05 to 5.0 g perlitre potassium chloride;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners.

In an embodiment, the first colon cleansing solution may be a solutionas commercialised under the tradename MOVIPREP®.

The first colon cleansing solution preferably includes a flavouringagent. The first colon cleansing solution preferably includes asweetener. Flavouring agents and sweeteners may be as describedhereinabove.

For example, a flavouring for use in in the first colon cleansingsolution should preferably mask saltiness, be relatively sweet but notexcessively so, and be stable in the composition. A flavouring makes thesolutions more palatable and thus aids patient compliance. Preferredflavourings include lemon e.g. Ungerer Lemon (available from UngererLimited, Sealand Road, Chester, England CH1 4LP) strawberry e.g. UngererStrawberry, grapefruit e.g. Ungerer Grapefruit flavouring powder,blackcurrant e.g. Ungerer Blackcurrant, pineapple e.g. IFF(International Flavours and Fragrances) Pineapple flavouring powder,orange eg Firmenich Orange, and vanilla/lemon and lime e.g. IFF Vanillaand Givaudin Roure Lemon and Lime Flav-o-lok, fruit punch eg Ungererfruit punch, citrus punch, mango, and berry. Those and further suitableflavourings are available from International Flavours and FragrancesInc. (Duddery Hill, Haverhill, Suffolk, CB9 8LG, England), Ungerer &Company (Sealand Road, Chester, England CH1 4LP) or Firmenich (FirmenichUK Ltd., Hayes Road, Southall, Middlesex UB2 5NN). More preferredflavourings are lemon, kiwi, strawberry grapefruit, fruit punch andmango. Fruit punch and mango are especially preferred flavours.

A particularly preferred flavouring is fruit punch flavour, for exampleat a level of 0.4 to 3.5 g per litre, for example 0.4 to 1.2 g perlitre, for example 0.938, 1.0 or 3.18 g per litre.

The first cleansing solution preferably includes a sweetener. Preferredsweeteners include aspartame, acesulfame potassium (acesulfame K),sucralose and saccharine, and/or combinations thereof. For example, thesolution may comprise one or both of aspartame and acesulfame potassium(acesulfame K). For example, it may comprise one or both of sucraloseand acesulfame potassium (acesulfame K). In a preferred embodiment, thesolution comprises aspartame or sucralose, for example sucralose.Preferred sweeteners include aspartame, acesulfame potassium (acesulfameK), sucralose and saccharine, and/or combinations thereof. For example,compositions of the invention may comprise one or both of aspartame andacesulfame potassium (acesulfame K). For example, compositions of theinvention may comprise one or both of sucralose and acesulfame potassium(acesulfame K). In a preferred embodiment, the solution comprisesaspartame or sucralose, for example aspartame.

Alternatively, compositions of the invention can be essentially freefrom added sweeteners, for example to minimize the number of differentcomponents in the compositions.

A souring agent (for example citric acid) may be present as a tasteenhancer. A souring agent is a component that imparts a sourness to acomposition. Other souring agents include malic acid, acetic acid,tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid,phytic acid, lactic acid or salts thereof. It may be present at a levelof from 0.1 to 3.0 g per litre, for example 0.3 to 2.0 g per litre, forexample 0.5 to 2.0 g per litre, for example 0.75 g, 1.0 g, 1.06 g, 1.25g or 1.5 g per litre. The souring agent (for example citric acid) may beprovided in an encapsulated form. The encapsulation provides a coatingthat isolates the souring agent from other components and from air andmoisture prior to its use. Several encapsulated forms of citric acid, orother souring agents, are commercially available. For example, theencapsulation may be with a water-soluble coating.

The amount of sweetener required depends on the nature and strength ofthe sweetener being considered. Typically, it is 0.10 to 4 g per litre.For example, the sweetener may be sucralose at 0.1 to 3.0 g per litre,for example 0.3 to 2.0 g per litre, for example 0.5 to 2.0 g per litre,for example 0.5 to 1.3 g per litre for example 0.63 g, 0.80 g, 1.0 g or1.58 g per litre.

The first cleansing solution may include one or more further optionalcomponents. Such components may be as set out above in section 3b).

In an embodiment, the first colon cleansing solution has a volume offrom 400 to 600 ml (for example 500 ml), and contains the quantities ofsolutes described in the section immediately above. For example thevolume may be 16 or 17 US fluid ounces. For example, the inventionprovides colon cleansing solution comprising:

(i) 175 to 220 g per litre PEG having an average molecular weight of2500 to 4500 Da.

(ii) 15 to 20 g per litre of one or more alkali metal sulphates,alkaline earth metal sulphates or a mixture thereof

(iii) 3.0 to 5.0 g per litre sodium chloride, and 1.5 to 2.5 g per litrepotassium chloride;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners.

Such a solution has a smaller volume than cleansing solutions that aregenerally used.

In an embodiment, the first colon cleansing solution is provided in avolume of from 300 ml up to 1200 ml. For example, the first solution mayhave a volume in a range with a lower limit of 300 ml, 400 ml, 500 ml,600 ml or 700 ml. Preferably, the lower limit is 500 ml, 600 ml or 700ml. The volume may be in a range with an upper limit of 1200 ml, 1100ml, 1000 ml, 900 ml or 800 ml. For example the volume may be in therange 400 ml to 1100 ml, for example 500 ml to 1000 ml, for example 600ml to 900 ml, for example 700 ml to 800 ml. For example, the first coloncleansing solution is provided in a volume of 750 ml. For example thevolume may be in the range 400 ml to 600 ml. For example, the firstcolon cleansing solution is provided in a volume of 500 ml. For exampleit may be in a volume of 16 or 17 US fluid ounces. The most appropriatevolume will depend on the exact components of the solution and theamounts in which they are present. In general, for a solution of higherosmotic strength, a smaller volume will be required.

The first cleansing solution may, for example, have a measuredosmolality in the range 200 to 2000 mOsmol/kg, 200 to 1500 mOsmol/kg. Ina preferred embodiment, it is hyper-osmotic. It may, for example have ameasured osmolality in the range 320 to 1500 mOsmol. For example, themeasured osmolality of the first cleansing solution is in the range 330to 1200 mOsmol/kg, for example 340 to 1000 mOsmol/kg, for example 350 to800 mOsmol/kg, for example 350 to 700 mOsmol/kg. For example, thesolutes in the solution may have a V(350) value of from 800 to 1600 ml,for example from 1000 to 1400 ml, for example from 1150 to 1250 ml, andbe in a volume of 400 to 600 ml, for example 500 ml.

The invention further provides a composition optionally presented in twoor more parts for the preparation of a first colon cleansing solution.For example the composition may comprise:

(i) 87.5 to 110 g PEG having an average molecular weight of 2500 to 4500Da.

(ii) 7.5 to 10 g of one or more alkali metal sulphates, alkaline earthmetal sulphates or a mixture thereof

(iii) 1.5 to 2.5 g sodium chloride and 0.75 to 1.25 g potassiumchloride;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners.

For example the composition may comprise:

(i) 100 g PEG having an average molecular weight of 3000 to 4000 Da.

(ii) 9.0 g sodium sulphate

(iii) 2.0 g sodium chloride and 1.0 g potassium chloride;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners.

For example, the flavouring and sweetener may be 0.469 g fruit punchflavouring, 0.476 g sucralose and 0.792 g citric acid. For example, theflavouring and sweetener may be 0.500 g fruit punch flavouring, 0.40 gsucralose and 0.75 g citric acid. For example, the flavouring andsweetener may be 1.43 g mango flavouring, 0.79 g sucralose and 1.74 gcitric acid. For example, the flavouring and sweetener may be 1.59 gfruit punch flavouring, 0.79 g sucralose and 1.74 g citric acid. Citricacid may optionally be packaged separately from the other components.

Particular first solutions S1 and S2, and particular second solutions T1and T2 are described in the examples section below. In a preferredaspect of the present invention, there is provided a method of cleansingthe colon of a subject comprising (or consisting essentially of):

administering to the subject a cleansing solution of S2 as set forthherein;

administering to the subject a cleansing solution of T1 as set forthherein.

In preferred embodiments of this aspect of the invention, the cleansingsolution of S2 is administered to the subject before the cleansingsolution of T1 is administered. It is particularly preferred that S2 isadministered to the subject and then, following a time interval (such asdisclosed herein), T1 is administered to the subject. In furtherpreferred embodiments of this aspect of the invention, additional fluid(such as clear fluid) is administered to the subject in conjunction withS2 and/or T1. For example, additional clear fluid (such as 500 ml orthereabout, or 1000 ml or thereabout) is administered to the subjectfollowing administration of S2 and/or T1. Alternatively, additionalclear fluid is administered to the subject during administration of S2and/or T1. In typical embodiments, the cleansing solution of S2 and/orT1 is self-administered.

7. USE OF SWEETENER IN COLON CLEANSING SOLUTION

It has been found by the current inventors that a sulphate-containingcolon cleansing solution that contains a souring agent (for examplecitric acid) and sucralose is particularly palatable.

The invention further provides, according to a fourth aspect, a coloncleansing solution comprising:

(i) 70 to 250 g per litre PEG having an average molecular weight of 2500to 4500 Da;

(ii) 2.0 to 20 g per litre of one or more alkali metal sulphates,alkaline earth metal sulphates or a mixture thereof;

(iii 1) optionally 1.0 to 5.0 g per litre sodium chloride;

(iii 2) optionally 0.5 to 1.5 (for example 0.5 to 1.1) g per litrepotassium chloride;

(iv) optionally one or more flavouring agents;

(v) sucralose; and

(vi) one or more souring agents.

Further, the invention provides a method for improving the palatabilityof a sulphate-containing colon cleansing solution comprising includingin the solution 0.1 to 3.0 g per litre sucralose and 0.1 to 4.0 g perlitre of souring agent, for example 0.1 to 3.0 g per litre of souringagent, for example citric acid. The invention provides a method fordiminishing the poor taste of a sulphate-containing colon cleansingsolution comprising including in the solution 0.1 to 3.0 g per litresucralose and 0.1 to 4.0 gof souring agent, for example 0.1 to 3.0 g perlitre of souring agent, for example citric acid.

It is postulated that the improved palatability is associated with areduced perceived saltiness of the solutions. The invention thusprovides a method for reducing the perceived saltiness of asulphate-containing colon cleansing solution comprising including in thesolution 0.1 to 3.0 g per litre sucralose and 0.1 to 4.0 g per litre ofsouring agent, for example 0.1 to 3.0 g per litre of souring agent, forexample citric acid. “Reduction” here is taken to mean as compared withan equivalent solution without the sucralose and souring agent.

A souring agent may be selected from citric acid, malic acid, aceticacid, tartaric acid, gluconodeltalactone, phosphoric acid, succinicacid, phytic acid, lactic acid or salts thereof. For example, thesouring agent may be citric acid. It may be present at a level of from0.1 to 4.0 g per litre, for example 0.1 to 3.0 g per litre, for example0.3 to 2.0 g per litre, for example 0.5 to 2.0 g per litre, for example0.75 g, 1.0 g, 1.06 g, 1.25 g or 1.5 g per litre. For example, it may beat a level of 3.0 to 4.0 g per litre, for example 3.48 g per litre.Citric acid, or another souring agent, may be provided in anencapsulated form. The encapsulation provides a coating that isolatesthe souring agent from other components and from air and moisture priorto its use. Several encapsulated forms of citric acid, or other souringagents, are commercially available. For example, the encapsulation maybe with a water-soluble coating.

The sucralose may, for example be present at a level of 0.1 to 3.0 g perlitre, for example 0.3 to 2.0 g per litre, for example 0.5 to 2.0 g perlitre, for example 0.5 to 1.3 g per litre for example 0.63 g, 0.80 g, or1.0 g per litre. For example, it may be at a level of 1.58 g per litre.

When sucralose and citric acid are used, a particularly preferredflavouring is fruit punch flavour, for example at a level of 0.4 to 1.2g per litre, for example 0.625 g per litre or 1.0 g per litre.

There is also provided a composition for the preparation of such asolution, for example by admixture with water. Preferred amounts of eachof components (i) to (iv) in the solutions and compositions of thefourth aspect of the invention are as set out for the first coloncleansing solutions and first colon cleansing compositions hereinabovein section 6b).

A colon cleansing solution according to the fourth aspect of theinvention may contain PEG, sulphate, sodium chloride, potassium chlorideand flavouring in amounts and types as described hereinabove in relationto the first colon cleansing solution in section 6b).

A colon cleansing solution according to the fourth aspect of theinvention may be used together with a solution of the first or secondaspect of the invention as set out in sections 2 to 5. Alternatively, itmay be used in combination with a different other colon cleansingsolution, or used in a suitable volume on its own. If used on its own,it may be used in a single dose or in a split dose administration. Theinvention provides a method of cleansing the colon of a subjectcomprising administering a solution of the fourth aspect of theinvention. The solution may be administered on its own or in combinationwith a further, different, solution.

8. KITS

a) kits providing a composition for the preparation of a solution of theinvention

As set out above in section 2d), the invention provides a compositionfor admixture with water (for example a dry composition, for example apowder), wherein the composition is optionally presented in two or moreparts and comprises the components of a solution of the invention. Ifthe components are provided in two or more parts, they may be providedin a kit. The invention thus provides a kit comprising:

a) 150 to 400 mmol ascorbate anion provided by a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) 5 to 100 g polyethylene glycol.

The kit may further comprise additional components as set out insections 3a), 3b) and 3d) above, and in the amounts set out there. Forexample, the kit may contain:

a) 150 to 400 mmol ascorbate anion provided by a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0;

b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da.

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents;

f) optionally one or more sweeteners.

Each of c) and d) may be present in the amounts described in section 3a)and 3d) above. Each of e) and f) may be as described above and/or be inthe amounts described in section 3a) and 3d) above.

In one embodiment, the kit contains:

a)

-   -   (i) 6.0 to 10 g ascorbic acid and    -   (ii) 40 to 60 g sodium ascorbate    -   the components (i) and (ii) being present in a weight ratio of        from 1:5063 to 1:7.875;

b) 30 to 50 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 1.5 to 4 g sodium chloride and 0.5 to 3.5 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

In an embodiment of a kit of the invention, the ascorbate component a)is packaged separately from the PEG component b). The remaining elementsmay be packaged together with the PEG component.

In an embodiment of a kit of the invention, the flavouring component e)or the sweetener component f) may be provided separately from othercomponents. The kit may provide several alternative flavourings,allowing the subject to decide themselves which flavouring from a rangeof flavourings to use.

For example, the kit may contain:

a)

-   -   (i) 7.54 g ascorbic acid and    -   (ii) 48.11 g sodium ascorbate

b) 40 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 3.20 g sodium chloride and 1.20 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners;

whereby component a) is packaged in a first compartment and componentsb), c) e) and f) are packaged in a second compartment.

One or more of the components may be in a dry powder form (for examplethe ascorbate component or the PEG component may be in dry powder form),whilst some of the remaining components (for example the sodium chlorideor the potassium chloride) are in the form of a tablet or in asemi-solid (for example gel) form. In such an embodiment, the subjectmay be instructed to dissolve the powder components in water and drinkit, and instructed to take the tablet or semi-solid form withoutdissolution. If a semi-solid form (for example gel) is present, thesubject may be instructed to add it to water before ingesting it, or thesubject may be instructed to take it as provided.

As set out above in section 5d), the invention provides a compositionfor admixture with water (for example a dry composition, for example apowder), wherein the composition is optionally presented in two or moreparts and comprises the components of a solution of the invention. Ifthe components are provided in two or more parts, they may be providedin a kit. The invention thus provides a kit comprising:

a) 180 to 220 mmol ascorbate anion provided by one or more salts ofascorbic acid; and

b) 5 to 100 g polyethylene glycol;

the kit being essentially free from ascorbic acid.

The kit may further comprise additional components as set out insections 5a), 5b) and 5d) above, and in the amounts set out there. Forexample, the kit may contain:

a) 180 to 220 mmol ascorbate anion provided by one or more salts ofascorbic acid;

b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da.

c) sodium chloride and potassium chloride;

d) optionally sodium sulphate;

e) optionally one or more flavouring agents;

f) optionally one or more sweeteners;

the kit being essentially free from ascorbic acid.

Each of c) and d) may be present in the amounts described in section 5a)and 5d) above. Each of e) and f) may be as described above and/or be inthe amounts described in section 5a) and 5d) above.

In one embodiment, the kit contains:

a) 35.65 to 43.55 g sodium ascorbate

b) 30 to 50 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 1.5 to 4 g sodium chloride and 0.5 to 3.5 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners;

the kit being essentially free from ascorbic acid.

In an embodiment of a kit of the invention, the ascorbate component a)is packaged separately from the PEG component b). The remainingcomponents may be packaged together with the PEG component.

In an embodiment of a kit of the invention, the flavouring component e)or the sweetener component f) may be provided separately from othercomponents. The kit may provide several alternative flavourings,allowing the subject to decide themselves which flavouring from a rangeof flavourings to use.

For example, the kit may contain:

a) 40 g sodium ascorbate

b) 40 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 2.50 g sodium chloride and 0.90 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners;

whereby component a) is packaged in a first compartment and componentsb), c) e) and f) are packaged in a second compartment.

In a further embodiment, one or more of the components may be in a drypowder form (for example the ascorbate component or the PEG componentmay be in dry powder form), whilst some of the remaining components (forexample the sodium chloride or the potassium chloride) are in the formof a tablet or in a semi-solid (for example gel) form. In such anembodiment, the subject may be instructed to dissolve the powdercomponents in water and drink it, and instructed to take the tablet orsemi-solid form without dissolution. If a semi-solid form (for examplegel) is present, the subject may be instructed to add it to water beforeingesting it, or the subject may be instructed to take it as provided.

It is convenient for the patient for a kit of the invention to beprovided in the form of, for example, a box. In a kit of the inventionthe first and/or second parts may each contained in one or morecontainers. Examples of suitable containers include tubs, bags andsachets. A preferred container is a sachet.

In one embodiment, the composition of the invention can be provided in amulti-chambered container, for example of the type disclosed inWO2012/105524. A multi-chambered container may have a partition wall andtwo separate powders can be stored separated from each other. Inaddition, in a container of the type disclosed in WO2012/105524, apowdered medicine, which has been stored in a separated state, can besimply and readily mixed at the time of use to provide an aqueoussolution.

For example, a multi-chambered container comprises a substantially flatpouch formed from a flexible film, a partition wall configured as adetachable seal detachably welding opposing inner surfaces of the pouch,and a pour port for infusion and discharge of a liquid, that is attachedto the periphery of the pouch so as to open into one of the plurality ofpartitioned chambers. For example, the partition wall comprises ahorizontal section which extends along a gusseted bottom section of thepouch and a perpendicular section which is curved from the horizontalsection to a pouch upper section. The partition wall may, for example,be frangible. For example, a first partitioned chamber having a largecapacity is formed on one side of the partition wall close to the bottomsection of the pouch, a second partitioned chamber having a smallcapacity is formed on the other side of the partition wall, and the pourport opens into the first partitioned chamber.

b) kits providing treatments according to the invention

As set out above in section 6), the invention provides varioussplit-dose treatments for colon cleansing in which the subject takes twodifferent agents. The invention thus provides a kit comprising:

-   -   a first colon cleansing agent, and    -   a second colon cleansing agent,

the second colon cleansing agent being a solution of the first or secondaspect of the invention described above.

The invention provides a kit comprising:

-   -   a first colon cleansing agent, and    -   a second colon cleansing agent,

the second colon agent solution being a solution in water of:

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) optionally 10 to 200 g per litre polyethylene glycol.

The invention also provides a kit comprising:

-   -   a first colon cleansing agent, and    -   a second colon cleansing agent,

the second colon cleansing agent being a solution in water of:

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid; and

b) optionally 10 to 200 g per litre polyethylene glycol;

the solution being essentially free from ascorbic acid.

In an embodiment, the first agent is different from the second.

A kit of the invention may provide compositions for the preparation ofthe colon cleansing solutions. The invention thus further provides a kitcomprising:

A) a first component, being a composition, optionally presented in twoor more parts for the preparation of a first colon cleansing solution asdescribed above by admixture with water; and

B) a second component, being a composition, optionally presented in twoor more parts for the preparation of a second colon cleansing solutionby admixture with water, the second colon cleansing solution being asolution as described hereinabove in relation to solutions and uses ofthe first or second aspects of the invention as set out in sections 2 to5.

Preferably, the first solution is of different composition from thesecond.

Accordingly, a kit of the invention may comprise:

A) a first component, being a composition optionally presented in two ormore parts for the preparation of a first colon cleansing solutioncomprising:

(i) 52.5 to 187.5 g PEG having an average molecular weight of 2500 to4500 Da.

(ii) 1.5 to 15 g of one or more alkali metal sulphates, alkaline earthmetal sulphates or a mixture thereof

(iii) optionally one or more electrolytes;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners,

and

B) a second component, being a composition optionally presented in twoor more parts for the preparation of a second colon cleansing solution,comprising

a) 150 to 400 mmol ascorbate anion provided by a mixture of:

-   -   (i) ascorbic acid and    -   (ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) optionally 5 to 100 g polyethylene glycol,

the first solution being different from the second.

A kit of the invention may comprise:

A) a first component, being a composition optionally presented in two ormore parts for the preparation of a first colon cleansing solutioncomprising:

(i) 52.5 to 187.5 g PEG having an average molecular weight of 2500 to4500 Da.

(ii) 1.5 to 15 g of one or more alkali metal sulphates, alkaline earthmetal sulphates or a mixture thereof

(iii) optionally one or more electrolytes;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners,

and

B) a second component, being a composition optionally presented in twoor more parts for the preparation of a second colon cleansing solution,comprising

a) 360 to 440 mmol ascorbate anion provided one or more salts ofascorbic acid; and

b) optionally 5 to 100 g polyethylene glycol,

the solution being essentially free from ascorbic acid;

the first solution being different from the second.

The first component may be a composition for the preparation of asolution as set out in section 6b) above. The first component preferablycomprises 97.5 to 187.5 g of PEG, for example 67.5 to 150 g of PEG, morepreferably 75 to 150 g, for example 90 to 112.5 g, for example 100 gPEG.

Preferably, the first component comprises a sulphate component (forexample sodium sulphate) in an amount of 1.5 to 11.25 g, for example3.75 to 11.25 g, for example 6 to 9 g, for example 6 or 9 g. Forexample, the first component comprises 6.0 to 15 g of one or more alkalimetal sulphates, alkaline earth metal sulphates or a mixture thereof.For example it comprises 9 g of sodium sulphate.

Preferably, the first component comprises sodium chloride in an amountof 0.375 to 3.75 g. For example, sodium chloride may be present in anamount of 0.75 to 3.0 g, for example 0.75 to 2.25 g, for example 1.125to 2.25 g, for example 1.5 to 2.25 g, for example 2.0 g.

For example, the first component comprises potassium chloride in anamount of 0.75 to 7.5 g. For example, potassium chloride may be presentin an amount of 0.0375 to 3.75 g, for example 0.075 to 2.25 g, forexample 0.15 to 1.5 g, for example 0.375 to 1.125 g, for example 0.375to 0.825 g, for example 1.0 g.

In an embodiment, the first component comprises sodium chloride andpotassium chloride. They can be present in the amounts mentionedimmediately above. For example, sodium chloride may be present in anamount of 1.125 to 2.25 g and potassium chloride may be present in anamount of 0.15 to 1.5 g; for example 2.0 g sodium chloride and 1.0 gpotassium chloride.

The second component of the kit of compositions of the invention ispreferably a composition for the preparation of a solution of the firstor second aspect of the invention as described hereinabove in sections 3or 5.

Accordingly, the kit may comprise:

A) a first component, being a composition optionally presented in two ormore parts for the preparation of a first colon cleansing solutioncomprising:

(i) 87.5 to 110 g PEG having an average molecular weight of 2500 to 4500Da.

(ii) 7.5 to 10 g of one or more alkali metal sulphates, alkaline earthmetal sulphates or a mixture thereof

(iii) 1.5 to 2.5 g sodium chloride and 0.75 to 1.25 g potassiumchloride;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners,

and

B) a second component, being a composition optionally presented in twoor more parts for the preparation of a second colon cleansing solution,comprising

a)

-   -   (i) 6.0 to 10 g ascorbic acid and    -   (ii) 40 to 60 g sodium ascorbate    -   the components (i) and (ii) being present in a weight ratio of        from 1:5063 to 1:7.875;

b) 30 to 50 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 1.5 to 4 g sodium chloride and 0.5 to 3.5 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

In an embodiment of a kit of the invention, in component B) theascorbate component a) is packaged separately from the PEG component b).The remaining elements of component B) may be packaged together with thePEG component.

For example, a kit may comprise:

A) a first component, being a composition optionally presented in two ormore parts for the preparation of a first colon cleansing solutioncomprising:

(i) 100 g PEG having an average molecular weight of 3000 to 4000 Da.

(ii) 9.0 g sodium sulphate

(iii) 2.0 g sodium chloride and 1.0 g potassium chloride;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners,

and

B) a second component for the preparation of a second colon cleansingsolution, comprising a)

-   -   (i) 7.54 g ascorbic acid and    -   (ii) 48.11 g sodium ascorbate

b) 40 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 3.20 g sodium chloride and 1.20 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners;

whereby component a) is packaged in a first compartment and componentsb), c) e) and f) are packaged in a second compartment.

For example, the flavouring and sweetener in the first component may be0.469 g fruit punch flavouring, 0.476 g sucralose and 0.792 g citricacid. For example, the flavouring and sweetener may be 0.500 g fruitpunch flavouring, 0.40 g sucralose and 0.75 g citric acid. For example,the flavouring and sweetener may be 1.43 g mango flavouring, 0.79 gsucralose and 1.74 g citric acid. For example, the flavouring andsweetener may be 1.59 g fruit punch flavouring, 0.79 g sucralose and1.74 g citric acid. Citric acid may optionally be packaged separatelyfrom the other components.

For example, the flavouring and sweetener in the second component may be0.60 g orange flavour and 1.93 g aspartame. For example, the flavouringand sweetener may be 1.60 g citrus flavour and 0.875 g aspartame. Forexample, the flavouring and sweetener may be 2.10 g orange grapefruitflavour and 0.875 g aspartame.

Alternatively, the kit may comprise:

A) a first component, being a composition optionally presented in two ormore parts for the preparation of a first colon cleansing solutioncomprising:

(i) 87.5 to 110 g PEG having an average molecular weight of 2500 to 4500Da.

(ii) 7.5 to 10 g of one or more alkali metal sulphates, alkaline earthmetal sulphates or a mixture thereof

(iii) 1.5 to 2.5 g sodium chloride and 0.75 to 1.25 g potassiumchloride;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners,

and

B) a second component, being a composition optionally presented in twoor more parts for the preparation of a second colon cleansing solution,comprising

a) 35.65 to 43.55 g sodium ascorbate

b) 30 to 50 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 1.5 to 4 g sodium chloride and 0.5 to 3.5 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners.

In an embodiment of a kit of the invention, in component B) theascorbate component a) is packaged separately from the PEG component b).The remaining elements of component B) may be packaged together with thePEG component.

For example, a kit may comprise:

A) a first component, being a composition optionally presented in two ormore parts for the preparation of a first colon cleansing solutioncomprising:

(i) 100 g PEG having an average molecular weight of 3000 to 4000 Da.

(ii) 9.0 g sodium sulphate

(iii) 2.0 g sodium chloride and 1.0 g potassium chloride;

(iv) optionally one or more flavouring agents; and

(v) optionally one or more sweeteners, and

B) a second component for the preparation of a second colon cleansingsolution, comprising a) 40 g sodium ascorbate

b) 40 g PEG having an average molecular weight of 3000 to 4000 Da;

c) 2.50 g sodium chloride and 0.90 g potassium chloride;

e) one or more flavouring agents; and

f) one or more sweeteners;

whereby component a) is packaged in a first compartment and componentsb), c) e) and f) are packaged in a second compartment.

For example, the flavouring and sweetener in the first component may be0.469 g fruit punch flavouring, 0.476 g sucralose and 0.792 g citricacid. For example, the flavouring and sweetener may be 0.500 g fruitpunch flavouring, 0.40 g sucralose and 0.75 g citric acid. For example,the flavouring and sweetener may be 1.43 g mango flavouring, 0.79 gsucralose and 1.74 g citric acid. For example, the flavouring andsweetener may be 1.59 g fruit punch flavouring, 0.79 g sucralose and1.74 g citric acid. Citric acid may optionally be packaged separatelyfrom the other components.

For example, the flavouring and sweetener in the second component may be0.80 g orange flavour and 1.10 g aspartame. For example, the flavouringand sweetener may be 1.60 g lemon/lime flavour and 1.625 g aspartame.For example, the flavouring and sweetener may be 2.15 g orangegrapefruit flavour and 1.625 g aspartame.

Preferably, the kit further comprises instructions for use. In anembodiment, a kit of the invention has instructions that instruct theuser of the volume to which each component is to be made up with water.For example, the specified volume of water for each solution is lessthan one litre. For example, the specified volume for the firstcomponent may be 300 ml to 1200 ml, for example 600 ml to 900 ml, forexample 750 ml; for example it may be a volume of 25 or 26 US fluidounces, for example 400 to 600 ml, for example 500 ml. For example itmay be a volume of 16 or 17 US fluid ounces. For example, the specifiedvolume for the second component may be from 250 ml to 1000 ml, forexample 400 ml to 700 ml, for example 500 ml. For example it may be avolume of 16 or 17 US fluid ounces. Further volumes that may bespecified in the instructions are the volumes set out hereinabove inrelation to the methods of the invention.

In general, the instructions specify that the first and second solutionsare to be ingested in succession with a time interval between them. Inan embodiment, the instructions specify that the first cleansingsolution is ingested first followed, after a time interval (for examplethe time between an evening and the following morning) by ingestion ofthe second cleansing solution. The time interval is preferably asdescribed above in relation to the methods of the invention. Theinstructions may specify that the components in the kit be made up intosolutions and then taken in accordance with the description set outabove in section 6 for the first solution and sections 3c) and 5c) forthe second solution.

For example, components A) and B) may be in dry powder, granular orother dry form. They may alternatively be in the form of concentrates orslurries. Components A) and B) may be in the same or different physicalforms. Components within A) and B) may be in the same or differentphysical forms. For example, one or both of components A) and B) are drypowders. A portion of either or each of components A) and B) may be inthe form of one or more solid tablets or capsules.

It is convenient for the patient for a kit of the invention to beprovided in the form of, for example, a box. In a kit of the inventionthe first and/or second components may each contained in one or morecontainers. In particular, the second component may be contained in morethan one container. For example, if the second component comprises bothascorbic acid and PEG then the ascorbic acid and PEG may be contained inseparate containers. The other constituents of the second component (forexample one or more of sodium chloride, potassium chloride and sodiumsulphate) may be in either of the separate containers. For example, theymay be in the container containing the PEG.

If a flavouring component is present in the first or second solution,then in a kit of the invention, the flavouring component for therelevant solution may be provided in a separate container from the otherconstituents of that solution.

Examples of suitable containers include tubs, bags and sachets. Apreferred container is a sachet.

In one embodiment, the composition of the invention can be provided in amulti-chambered container, for example of the type disclosed inWO2012/105524, as described above in section 8a).

In one embodiment, a kit comprises:

A) a first sachet comprising a first composition for the preparation ofthe first cleansing solution;

B1) a second sachet;

B2) a third sachet;

wherein the second and third sachets together provide a composition forthe preparation of the second cleansing solution.

For example, in a kit of the invention as mentioned immediately above:

A) the first sachet comprises polyethylene glycol and/or sodiumsulphate;

B1) the second sachet comprises one or more components selected frompolyethylene glycol, one or more alkali metal sulphates, alkaline earthmetal sulphates or a mixture thereof and electrolytes; and

B2) the third sachet comprises one or more salts of ascorbic acid and,if appropriate, ascorbic acid;

the contents of sachets (B1) and (B2) together providing the componentsfor the second cleansing solution.

For example, in a further embodiment of a kit of the invention, ratherthan being provided within a first sachet (A) with the PEG, some or allof the sulphate(s), electrolytes, flavouring agents and sweeteners areprovided in the form of a tablet or capsule. In a further embodiment ofa kit of the invention, rather than being provided within a second orthird sachet (B1 or B2) with the PEG, ascorbic acid or ascorbatecomponent, some or all of the sulphate(s), electrolytes, flavouringagents and sweeteners are provided in the form of a tablet or capsule.

A kit may contain one treatment, for example a cleansing treatment, orseveral treatments. A treatment generally comprises one dose of thefirst cleansing solution (or components for preparing the firstcleansing solution) and one dose of the second cleansing solution (orcomponents for preparing the first cleansing solution). In a kit of theinvention, preferably the first component comprises one dose of thefirst cleansing solution, and the second component comprises one dose ofthe second cleansing solution.

A kit of the invention may be for use in a method of cleansing the coloncomprising:

-   -   the subject taking an effective amount of a first colon        cleansing solution as described herein; and

then

-   -   the subject taking an effective amount of a second colon        cleansing solution as described herein.

9. ALTERNATIVE COLON CLEANSING REGIMENS

a) General

The solutions and compositions of the first and second aspects of theinvention described above in sections 2 to 5 find further use in splitdose colon cleansing treatments in which the subject takes two differentsolutions (a first colon cleansing solution, followed by a second coloncleansing solution) in which the solution of the first or second aspectof the invention is the first colon cleansing solution. In a fifthaspect, the invention thus provides a method of cleansing the colon of amammal comprising:

-   -   the subject taking an effective amount of a first colon        cleansing solution; and then    -   the subject taking an effective amount of a second colon        cleansing solution,

the first colon cleansing solution being a solution of the first orsecond aspect of the invention described above in sections 2 to 5.

The invention also provides a method of cleansing the colon of a mammalcomprising:

-   -   the subject taking an effective amount of a first colon        cleansing solution; and then    -   the subject taking an effective amount of a second colon        cleansing solution, the first colon cleansing solution being a        solution comprising

a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of:

(i) ascorbic acid and

(ii) one or more salts of ascorbic acid

the components (i) and (ii) being present in a molar ratio of from 1:4.5to 1:7.0; and

b) optionally 10 to 200 g per litre polyethylene glycol.

The invention also provides a method of cleansing the colon of a mammalcomprising:

-   -   the subject taking an effective amount of a first colon        cleansing solution; and then    -   the subject taking an effective amount of a second colon        cleansing solution,

the first colon cleansing solution being a solution comprising

a) 360 to 440 mmol per litre ascorbate anion provided by one or moresalts of ascorbic acid; and

b) optionally 10 to 200 g per litre polyethylene glycol;

the solution being essentially free from ascorbic acid.

The solutions and methods of the fifth aspect of the invention may havethe features described above in relation to the solutions and methods ofthe third aspect of the invention as set out in section 6 above.

b) alternative:

The invention also provides a method of cleansing the colon of a subjectcomprising:

-   -   administering to the subject an effective amount of a first        cleansing solution; and then after a time interval    -   administering to the subject an effective amount of a second        cleansing solution,

wherein the first cleansing solution is hyper-osmotic and containsascorbic acid, one or more salts of ascorbic acid, or a mixture thereof(for example ascorbic acid and sodium ascorbate, for example sodiumascorbate); and wherein the second cleansing solution is eithersubstantially free from ascorbic acid and salts thereof, or containsascorbic acid, one or more salts of ascorbic acid, or a mixture thereof,in an amount providing a lower concentration of ascorbate anion than ispresent in the first cleansing solution. The first cleansing solutionmay comprise PEG and electrolytes (for example sodium chloride andpotassium chloride). The second solution may comprise PEG; it maycomprise an alkali metal or alkaline earth metal sulphate (for examplesodium sulphate); it may comprise electrolytes (for example sodiumchloride and potassium chloride). There are also provided kitscomprising a first and a second solution according to the invention, andkits comprising compositions for preparing the first and secondsolutions.

The first cleansing solution contains a higher concentration ofascorbate anion than is present in the second cleansing solution. Forexample, the first cleansing solution contains twice the concentrationof the ascorbate anion than the second cleansing solution or more. Forexample, the first solution contains three times or more, four times ormore, or five times or more the concentration of the ascorbate anionthan the second cleansing solution. For example, the first cleansingsolution contains a concentration of the ascorbate anion that is atleast 50 mmol per litre greater than that of the second cleansingsolution. That is to say that the first solution contains aconcentration of ascorbate anion that is at least 50 mmol per litregreater than that of the second solution. For example, the firstsolution contains a concentration of the ascorbate anion that is greaterby at least 100 mmol per litre, for example at least 200 mmol per litre,at least 300 mmol per litre.

For example, the second cleansing solution may be substantially freefrom an ascorbate component.

For example, the first cleansing solution may comprise:

-   -   56.6 g sodium ascorbate, or    -   33.9 g sodium ascorbate and 20.1 g ascorbic acid, or    -   33.9 g sodium ascorbate, or    -   33.9 g sodium ascorbate and 21.4 g magnesium ascorbate.

The first cleansing solution may further comprise polyethylene glycol.The polyethylene glycol (PEG) may, for example, have an averagemolecular weight of 2500 to 4500 Da, for example 3000 to 4000 Da. Forexample, the PEG may be PEG 3350 or PEG 4000 as defined in nationalpharmacopeias. Further examples of suitable PEGs recognized in somenational pharmacopeias include Macrogols, for example Macrogol 4000.

For example, the first cleansing solution may comprise 20 g or 40 g PEG3350. For example, the first cleansing solution may have a volume of 500ml. For example it may have a volume of 16 or 17 US fluid ounces.

The second cleansing solution may comprise polyethylene glycol and/or analkali metal sulphate, an alkaline earth metal sulphate, or a mixturethereof.

The polyethylene glycol (PEG) in the second cleansing solution may be asdescribed immediately above for the first cleansing solution. The PEG inthe second cleansing solution can be a different PEG from the PEG in thesecond cleansing solution. For example, one PEG may be PEG3350 and theother PEG may be PEG4000. For example, the second cleansing solution maycomprise 100 g PEG 3350. For example, the second cleansing solution mayhave a volume of 750 ml. For example it may have a volume of 25 or 26 USfluid ounces.

The second cleansing solution preferably comprises an alkali metalsulphate, an alkaline earth metal sulphate or a mixture thereof. Analkali metal or alkaline earth metal sulphate may, for example, beselected from sodium sulphate, potassium sulphate and magnesiumsulphate. The solution may comprise more than one of sodium sulphate,potassium sulphate and magnesium sulphate, for example all three.Preferably, the alkali metal sulphate, an alkaline earth metal sulphateor the mixture thereof is or includes sodium sulphate. Preferably, analkali metal sulphate or alkaline earth metal sulphate (for examplesodium sulphate) is anhydrous.

For example, the second cleansing solution may have a volume of 750 mland comprise 3 g, 6 g or 9 g of sodium sulphate.

The first and/or second cleansing solution(s) may further comprise oneor more of:

a) one or more electrolytes;

b) one or more flavouring agents;

c) one or more sweeteners.

Electrolytes include salts of sodium, potassium, calcium and magnesium,particularly sodium and potassium; and salts of chloride, iodide,bicarbonate and carbonate, particularly chloride. Preferred electrolytesare sodium chloride and potassium chloride. In an embodiment, the firstand/or second solution is substantially free from sodium bicarbonate.

For example, the second cleansing solution may have a volume of 750 mland comprise 1.4 g sodium chloride and 0.3 g potassium chloride; or 1.6g sodium chloride and 0.7 g potassium chloride; or 2.0 g sodium chlorideand 1.0 g potassium chloride.

For example, the first cleansing solution may have a volume of 500 mland comprise 3.5 g sodium chloride and 2.2 g potassium chloride; or 2.7g sodium chloride and 1.3 g potassium chloride; or 2.8 g sodium chlorideand 1.3 g potassium chloride; or 2.8 g sodium chloride and 2.0 gpotassium chloride; or 3.1 g sodium chloride and 1.3 g potassiumchloride. For example the first cleansing solution is substantially freefrom sodium bicarbonate.

The first and/or second cleansing solution(s) preferably include aflavouring agent. Flavouring for use in compositions of the inventionshould preferably mask saltiness, be relatively sweet but notexcessively so, and be stable in the composition. Flavouring makes thesolutions more palatable and thus aids patient compliance. Preferredflavourings include lemon e.g. Ungerer Lemon (available from UngererLimited, Sealand Road, Chester, England CH1 4LP) strawberry e.g. UngererStrawberry, grapefruit e.g. Ungerer Grapefruit flavouring powder,blackcurrant e.g. Ungerer Blackcurrant, pineapple e.g. IFF(International Flavours and Fragrances) Pineapple flavouring powder,orange eg Firmenich Orange, vanilla/lemon and lime e.g. IFF Vanilla andGivaudin Roure Lemon and Lime Flav-o-lok, fruit punch eg Ungerer fruitpunch, citrus punch, mango, and berry. Those and further suitableflavourings are available from International Flavours and FragrancesInc. (Duddery Hill, Haverhill, Suffolk, CB9 8LG, England), Ungerer &Company (Sealand Road, Chester, England CH1 4LP) or Firmenich (FirmenichUK Ltd., Hayes Road, Southall, Middlesex UB2 5NN). More preferredflavourings are lemon, kiwi, strawberry, grapefruit, orange, fruit punchand mango.

Fruit punch and mango are especially preferred flavourings for the firstsolution. The most preferred flavourings for the second solution arelemon flavour and orange flavour.

The first and/or second cleansing solution(s) preferably include asweetener. Sugar-based sweeteners are generally not suited for coloncleansing compositions because the delivery of unabsorbed sugars to thecolon provides a substrate for bacteria. Such sugars may be metabolisedby the bacteria to form explosive gases such as hydrogen and methane.The presence of explosive gases in the colon can be highly dangerouswhen electrical apparatus is to be used during colonoscopy or otherprocedures.

Preferred sweeteners include aspartame, acesulfame potassium (acesulfameK), sucralose and saccharine, and/or combinations thereof. For example,compositions of the invention may comprise one or both of aspartame andacesulfame potassium (acesulfame K). For example, compositions of theinvention may comprise one or both of sucralose and acesulfame potassium(acesulfame K). Alternatively, compositions of the invention can besubstantially free from added sweeteners, for example to minimize thenumber of different components in the compositions. Citric acid may alsobe present as a taste enhancer.

EXAMPLES General Description of Sample Evaluation Protocol

The same sample evaluation protocol was used for the taste tests of allof the solutions described below that were taste tested. The protocolwas as follows:

1. The solution was sipped from 1 oz cups, swished in the mouth, andexpectorated.

2. Initial flavour was immediately evaluated (t=0).

3. The aftertaste was evaluated at periodic time intervals: 1, 3 and 5minutes.

4. Upon completing the evaluation, the panellists cleansed their palatesusing spring water and unsalted crackers.

The Panelists were asked to provide a score of their perception of theintensity of the saltiness of the solutions, using the scale:

Intensity Scale: 0=None

-   -   1=Slight    -   2=Moderate    -   3=Strong

In general the panel consisted of from 2 to 8 tasters. The averagesaltiness intensity score was plotted against time.

Example 1 Sodium Ascorbate/Ascorbic Acid Solutions

In an initial set of solutions containing PEG3350 (40 g), sodiumchloride (2.8 g), potassium chloride (1.3 g) and sodium ascorbate (56.6g), it was found that the sweeteners sucralose and aspartame were mosteffective in reducing the perceived saltiness of the solution.Acesulfame-K and sodium saccharin were less effective.

The solutions in Tables 1 and 2 were prepared and taste tested. Theresults of the taste testing are shown in FIGS. 1 and 2.

TABLE 1 Aspartame-containing solutions Water Sodium Ascorbic Molar toVol/ Sol'n PEG3350/g NaCl/g KCl/g Aspartame/g Ascorbate/g Acid/g ratioml F1 40 2.8 1.3 0 56.60 0 100:0  500 F2 40 2.8 1.3 2.0 56.60 0 100:0 500 F3 40 2.8 1.3 2.0 39.62 15.10 70:30 500 F4 40 2.8 1.3 2.0 45.2810.06 80:20 500 F5 40 2.8 1.3 2.0 48.11 7.55 85:15 500 F6 40 2.8 1.3 2.050.94 5.03 90:10 500

TABLE 2 Sucralose-containing solutions Water Sodium Ascorbic Molar toVol/ Sol'n PEG3350/g NaCl/g KCl/g Sucralose/g Ascorbate/g Acid/g ratioml G1 40 2.8 1.3 0 56.60 0 100:0  500 G2 40 2.8 1.3 1.5 56.60 0 100:0 500 G3 40 2.8 1.3 1.5 39.62 15.10 70:30 500 G4 40 2.8 1.3 1.5 45.2810.06 80:20 500 G5 40 2.8 1.3 1.5 48.11 7.55 85:15 500 G6 40 2.8 1.3 1.550.94 5.03 90:10 500

In FIGS. 1 and 2, it is seen that the saltiness intensity is reducedmost in the solution containing sodium ascorbate and ascorbic acid inthe ratio 85:15, ie solutions F5 and G5.

Example 2 Sodium Ascorbate Solutions and Taste Testing

The solutions in Table 3 were prepared and taste tested. The results ofthe taste testing are shown in FIG. 3.

TABLE 3 Sodium ascorbate solutions Water PEG3350/ NaCl/ Sodium to Sol'ng g KCl/g Aspartame/g Ascorbate/g Vol/ml H1 40 2.8 1.3 0 56.6 500 H2 402.8 1.3 0 40 500 H3 40 2.8 1.3 1.00 40 500 H4 40 2.8 1.3 1.25 40 500 H540 2.8 1.3 1.50 40 500

In FIG. 3, it is seen that the saltiness intensity is reduced bydecreasing the amount of sodium ascorbate in the solution (compare H1 vsH2). It is further seen that the saltiness is reduced most by 1.25 g/500ml of aspartame.

Example 3 PEG-Electrolyte Solutions and Taste Testing

In an initial set of solutions containing PEG3350 (100 g), sodiumsulphate (9.0 g), sodium chloride (1.4 g), potassium chloride (0.3 g),it was found that the sweeteners sucralose (0.1%), aspartame (0.4%) or amixture of the two (sucralose 0.07%/aspartame 0.12%) were most effectivein reducing the perceived saltiness of the solution. Acesulfame-K,sodium saccharin and other mixtures were less effective.

The solutions in Table 4 were prepared and taste tested. The results ofthe taste testing are shown in FIG. 4.

TABLE 4 PEG-electrolyte solutions Citric Water to Sol'n PEG3350/gNa₂SO₄/g NaCl/g KCl/g Sucralose/g Acid/g Vol/ml I1 100.0 9.0 1.4 0.3 0 0500 I2 100.0 9.0 1.4 0.3 0.50 0 500 I3 100.0 9.0 1.4 0.3 0.50 0.375 500I4 100.0 9.0 1.4 0.3 0.50 0.50 500 I5 100.0 9.0 1.4 0.3 0.50 0.625 500

The results of the taste testing are shown in FIG. 4. It is seen thatthe solutions containing citric acid were perceived as less salty thanthe solutions without citric acid.

Example 4 Bowel Cleansing Solutions

The following bowel cleansing solutions of the invention were prepared.For solution S1, the components shown in Table 5 were combined in drypowder form and sealed in respective sachets A and B as indicated in thetable. The solution was then prepared by dissolving the contents inwater to the volume stated in the penultimate column. Solution S2 wasprepared in an analogous manner.

TABLE 5 Sachet A Fruit Sachet B Water Na₂SO₄ Punch Citric to Vol/V(350)/ Sol'n PEG3350/g (anhyd)/g NaCl/g KCl/g Sucralose/g Flavouring/gAcid/g ml ml S1 100.00 9.00 2.00 1.00 0.476 0.469 0.792 750 1180 S2100.00 9.00 2.00 1.00 0.40 0.500 0.75 500 1210

For solution T1, the components shown in Table 6 were combined in drypowder form and sealed in respective sachets C and D as indicated in thetable. The solution was then prepared by mixing the contents of the twosachets together and then dissolving them in water to the volume statedin the penultimate column. Solution T2 was prepared in an analogousmanner.

TABLE 6 Sachet C Sachet D Water Orange Sodium Ascorbic to Vol/ V(350)/Sol'n PEG3350/g NaCl/g KCl/g Aspartame/g Flavour/g Ascorbate/g Acid/g mlml T1 40.00 3.20 1.20 1.93 0.60 48.11 7.54 500 1850 T2 40.00 2.50 0.901.10 0.80 40.00 0 500 1500

Example 4a V(350) Osmolality Measurements

In order to assess the osmotic strength of the solutions, it wasdetermined how much water was required to provide a solution withmeasured osmolality of 350 mOsmol/kg from the amounts of the componentsin Tables 5 and 6.

To each solution prepared by dissolving the components in Tables 5 and 6above in 500 ml of deionised water was added further deionised wateruntil it reached an osmolality of 350 mOsmol/kg. The total volumes(including the initial 500 ml) required to reach an osmolality of 350mOsmol/kg are recorded in Tables 5 and 6 in the final columnsOsmolalities were measured using an Advanced Instruments, Inc Model 3250osmometer. The osmometer was operated following standard instructions:after the device passes a calibration check, the “Low Range” osmolalityrange (0 to 2000 mOsmol/kg) is selected, and a sample tube containing250 μl of sample solution is placed in the freezing chamber. The “start”button is then pressed. When the measurement is completed, the devicedisplays the measurement result and that is recorded.

Example 4b Bowel Cleansing

In a bowel cleansing study, subjects are given solutions S1 or S2 in anevening followed by T1 or T2 the following morning. In a variant,subjects are given solution T1 or T2 in an evening followed by S1 or S2the following morning.

Each subject receives the solution regimen in the split dose intake:

-   -   Evening dose: Day 1; start intake between 17:00 and 18:00 for an        intake period of up to 2 hours after fasting from 14:00 hours.    -   Morning dose: Day 2; start intake between 07:00 and 08:00 for an        intake period of 2 hours. Following each dose additional clear        liquid will be consumed to make the total dose and additional        clear fluid ingested equal to at least 3 L in the case of Arms 1        to 6, 8 and 9, and at least 2 L in the case of Arm 7.

Each dose of cleansing solution is reconstituted with water from theappropriate pair of sachets containing powder for oral solution. Thecleansing solution can be cooled in the fridge based on subjectpreference. Evening cleansing solution dose is drunk within 2 hoursafter the start of the intake on the evening of Day 1. At least theindicated additional clear fluid is also consumed, preferably within 1hour after the end of intake of cleansing solution in the evening.

In the morning of Day 2, the second dose is drunk within 2 hours afterthe start of intake. At least the indicated additional clear fluid isalso consumed, preferably within 1 hour after the end of intake ofcleansing solution in the morning. The total duration of each intake ofcleansing solution and clear fluid intake should normally not exceed 3hours. Each subject is instructed to drink the assigned cleansingsolutions as 100 mL fractions every 10 minutes. The mandatory additionalclear liquid intake (water) after the cleansing solution intake can betaken by the subject as prefers, usually within 1 hour after completionof each cleansing solution intake. The start time and finish time ofintake is recorded. The volume of any cleansing solution or additionalclear fluid left in the respective containers is measured. In arms 6 to9 the volume of fluid consumed ad libitum is monitored and recorded.

TABLE 7 Arm Arm 1 Arm 2 Arm 3 Arm 4 Arm 5 Evening S1 (750 ml) T1 (500ml) S2 (500 ml) MOVIPREP T1 (500 ml) 875 ml 875 ml 1000 ml (1000 ml)1000 ml additional clear additional clear additional clear 500 mladditional clear fluid fluid fluid additional clear fluid fluid MorningT1 (500 ml) S1 (750 ml) T1 (500 ml) MOVIPREP S2 (500 ml) 875 ml 875 ml1000 ml (1000 ml) 1000 ml additional clear additional clear additionalclear 500 ml additional clear fluid fluid fluid additional clear fluidfluid

TABLE 8 Arm Arm 6 Arm 7 Arm 8 Arm 9 Evening S2 (500 ml) S2 (500 ml) S2(500 ml) MOVIPREP Additional clear Additional clear Additional clear(1000 ml) fluid: minimum fluid: minimum fluid: minimum additional clear1000 ml or more ad 500 ml, or more ad 1000 ml or more ad fluid: minimumlib. lib lib 500 ml or more ad lib Morning T1 (500 ml) T1 (500 ml) T2(500 ml) MOVIPREP Additional clear Additional clear Additional clear(1000 ml) fluid: minimum fluid: minimum fluid: minimum additional clear1000 ml or more ad 500 ml, or more ad 1000 ml or more ad fluid: minimumlib lib lib 500 ml or more ad lib

Stool output is measured from the start of the intake on the evening ofDay 1 and over the following 24 hours. “Stool” is the term used to referto all bowel effluent. Mostly, it is liquid. The following are alsoassessed

-   -   Tolerability (vomiting rate).    -   Time and volume of cleansing solution to reach a clear effluent.

In certain subjects, the following are also assessed:

-   -   Colon cleansing success.    -   The segmental cleansing scores for each of the five colon        segments.    -   Pharmacokinetic evaluation of key active ingredients: Ascorbate        components and their metabolite (oxalic acid) in blood, urine        and faeces and PEG3350 and electrolytes in faeces at defined        time points, to demonstrate biological activities. Electrolytes        in blood and urine are quantified using standard clinical        chemistry methods.

The study described above was carried out in two parts: Parts A and B.

Part A:

In the part A, 120 subjects (70 male, 50 female) were allocated to thefour study Arms, Arms 1 to 4. They were given the solutions as set outin Table 7. At the time of filing, the full statistical analysis of theresults is not complete. The interim results based on a preliminaryanalysis of the data and available at the time of filing are shown inTable 9.

TABLE 9 Arm Arm 1 Arm 2 Arm 3 Arm 4 Number of subjects 30 30/29* 3030/29* Mean Stool Weight (g) 2951 g 3219 g 3399 g 2491 g Stool Weight90% 2680 g-3222 g 2963 g-3475 g 3221 g-3578 g 2213 g-2769 g confidenceinterval (g) Protocol total IMP 1250 ml 1250 ml 1000 ml 2000 ml volumeProtocol total additional 1750 ml 1750 ml 2000 ml 1000 ml clear fluidvolume Vomiting rate 1 (3.33%) 3 (10%) 1 (3.33%) 1 (3.33%)

Overall, the compliance level was good. However, in each of Arms 2 and4, 30 subjects began the study, but one subject left the study afterconsuming the first solution, and before any stool sample could becollected (thus 29 subjects are indicated (*)). The stool weight dataare based on the set of 30 subjects for Arms 1 and 3, and on the set of29 subjects for Arms 2 and 4. Both of those subjects who left the studyhad the symptom of vomiting. They are included in the vomiting rateresults.

It is seen that in each of Arms 1, 2 and 3 the subjects achieved ahigher mean stool output weight than in Arm 4, which represents a priorart colon cleansing solution. This was achieved with the subjects ineach of Arms 1, 2 and 3 consuming a lower total volume of bowelcleansing solution (investigational medicinal product “IMP”) than in Arm4. The vomiting rate for Arm 2 was higher than for the other arms. Thevomiting rate for each of the solutions was within expected limits for abowel cleansing solution.

Part B:

In part B, 120 subjects (54 male, 66 female) were allocated to the fourstudy Arms, Arms 6 to 9. They were given the solutions as set out inTable 8. Mean stool output was highest in Arm 7 and slightly lower inArm 6. Arm 8 gave a lower mean stool output, but all of Arms 6, 7 and 8gave a higher mean stool output than Arm 9, which represents a prior artcolon cleansing solution. Mean stool output exceeded 2400 g in all arms.Mean stool output in Arms 6 and 7 exceeded 3000 g.

The subjects in part B underwent colonoscopy and the quality ofcleansing was graded by the colonoscopist, who was not aware of whichcleansing treatment had been administered. Grading used the HarefieldCleansing Scale. For details of the Harefield Cleansing Scale, seeHalphen et al., Gastrointestinal Endoscopy, 2013, 78, 121-131. TheHarefield Cleansing Scale grades colon cleansing as Grade A, B, C or D,A being the best. Grades A and B are considered a successful cleansing;Grades C and D are considered an unsuccessful cleansing. At the time offiling, the full statistical analysis of the results is not complete.The interim results based on a preliminary analysis of the data andavailable at the time of filing are shown in Table 10.

TABLE 10 Arm Arm 6 Arm 7 Arm 8 Arm 9 Number of subjects 30 30 30 30Protocol total IMP volume 1000 ml 1000 ml 1000 ml 2000 ml Protocolminimum total 2000 ml 1000 ml 2000 ml 1000 ml additional clear fluidvolume Grade A 22 28 20 6 Grade B 8 2 7 21 Grade C 0 0 3 2 Grade D 0 0 01

It is seen in Table 10 that there was a higher proportion of Grade Acleansing in each of Arms 6, 7 and 8 than in Arm 9. This was achievedwith the subjects in each of Arms 6, 7 and 8 consuming a lower totalvolume of bowel cleansing solution (investigational medicinal product“IMP”) than in Arm 9.

Example 5 Bowel Cleansing Solutions

The following bowel cleansing solutions of the invention are prepared.For solution S3, the components shown in Table 11 are combined in drypowder form and sealed in respective sachets A and B as indicated in thetable. The solution is then prepared by dissolving the contents in waterto the volume stated in the far right-hand column. Solution S4 isprepared in an analogous manner

TABLE 11 Sachet A Fruit Sachet B Water Na₂SO₄ Mango Punch Citric to Vol/Sol'n PEG3350/g (anhyd)/g NaCl/g KCl/g Sucralose/g Flavouring/gFlavouring/g Acid #/g ml S3 100.00 9.00 2.00 1.00 0.79 1.43 — 1.74 500S4 100.00 9.00 2.00 1.00 0.79 — 1.59 1.74 500 # citric acid encapsulatedwith water soluble coating

For solution T3, the components shown in Table 12 are combined in drypowder form and sealed in respective sachets C and D as indicated in thetable. The solution is then prepared by mixing the contents of the twosachets together and then dissolving them in water to the volume statedin the far right-hand column. Solutions T4, T5 and T6 are prepared in ananalogous manner.

TABLE 12 Sachet C Orange Sachet D Water Citrus Gr'fruit Sodium Ascorbicto Vol/ Sol'n PEG3350/g NaCl/g KCl/g Aspartame/g Flavour/g flavourAscorbate/g Acid/g ml T3 40.00 3.20 1.20 0.875 1.6 — 48.11 7.54 500 T440.00 3.20 1.20 0.875 — 2.1 48.11 7.54 500

TABLE 13 Sachet C Lemon/ Sachet D Water Lime Orange Sodium Ascorbic toVol/ Sol'n PEG3350/g NaCl/g KCl/g Aspartame/g Flavour/g flavourAscorbate/g Acid/g ml T5 40.00 2.50 0.90 1.625 1.6 — 40.00 — 500 T640.00 2.50 0.90 1.625 — 2.15 40.00 — 500

We claim:
 1. A kit comprising: A) a first component, being a compositionoptionally presented in two or more parts for the preparation of a firstcolon cleansing solution comprising: (I) 52.5 to 187.5 g PEG having anaverage molecular weight of 2500 to 4500 Da. (II) 1.5 to 15 g of one ormore alkali metal sulphates, alkaline earth metal sulphates or a mixturethereof (III) optionally one or more electrolytes; (IV) optionally oneor more flavouring agents; and (V) optionally one or more sweeteners,and B) a second component, being a composition optionally presented intwo or more parts for the preparation of a second colon cleansingsolution, comprising a) 150 to 400 mmol ascorbate anion provided by amixture of: (i) ascorbic acid and (ii) one or more salts of ascorbicacid the components (i) and (ii) being present in a molar ratio of from1:4.5 to 1:7.0; and b) 5 to 100 g polyethylene glycol having an averagemolecular weight of 2500 to 4500 Da, the first solution being differentfrom the second.
 2. A kit as claimed in claim 1 wherein the firstcomponent comprises 90 to 112.5 g PEG.
 3. A kit as claimed in claim 1wherein the first component comprises 6.0 to 15 g sodium sulphate.
 4. Akit as claimed in claim 1 wherein the first component comprises 1.5 to2.25 g sodium chloride.
 5. A kit as claimed in claim 1 wherein the firstcomponent comprises 0.375 to 1.125 g potassium chloride.
 6. A kit asclaimed in claim 1 wherein the first component comprises: (I) 100 g PEGhaving an average molecular weight of 3000 to 4000 Da. (II) 9 g sodiumsulphate; (III) 2.0 g sodium chloride and 1.0 g potassium chloride; (IV)one or more flavouring agents; and (V) one or more sweeteners,
 7. A kitas claimed in claim 6 wherein the flavouring agent is mango, and thesweetener is sucralose.
 8. A kit as claimed in claim 7 wherein the firstcomponent further comprises citric acid as a taste enhancer.
 9. A kit asclaimed in claim 1 wherein the first component is in dry powder form.10. A kit as claimed in claim 1 wherein in the second component B) theascorbate component a) is packaged separately from the PEG component b).11. A kit as claimed in claim 1 wherein the second component comprises6.0 to 10 g ascorbic acid and 40 to 60 g sodium ascorbate.
 12. A kit asclaimed in claim 1 wherein the second component comprises 30 to 50 gPEG.
 13. A kit as claimed in claim 1 wherein the second componentcomprises 2.0 to 3.5 g sodium chloride.
 14. A kit as claimed in claim 1wherein the second component comprises 0.75 to 1.5 g potassium chloride.15. A kit as claimed in claim 1 wherein the second component comprisesa) (i) 7.54 g ascorbic acid and (ii) 48.11 g sodium ascorbate b) 40 gPEG having an average molecular weight of 3000 to 4000 Da; c) 3.20 gsodium chloride and 1.20 g potassium chloride; e) one or more flavouringagents; and f) one or more sweeteners; wherein component a) is packagedin a first compartment and components b), c) e) and f) are packaged in asecond compartment.
 16. A kit as claimed in claim 15 wherein thesweetener is aspartame and the flavouring is selected from lemon, kiwi,strawberry, grapefruit, orange, fruit punch and mango.
 17. A kit asclaimed in claim 1 wherein the second component is in dry powder form.18. A kit comprising: A) a first component, being a compositionoptionally presented in two or more parts for the preparation of a firstcolon cleansing solution comprising: (I) 100 g PEG having an averagemolecular weight of 3000 to 4000 Da. (II) 9.0 g sodium sulphate (III)2.0 g sodium chloride and 1.0 g potassium chloride; (IV) one or moreflavouring agents; and (V) one or more sweeteners, and B) a secondcomponent for the preparation of a second colon cleansing solution,comprising a) (i) 7.54 g ascorbic acid and (ii) 48.11 g sodium ascorbateb) 40 g PEG having an average molecular weight of 3000 to 4000 Da; c)3.20 g sodium chloride and 1.20 g potassium chloride; e) one or moreflavouring agents; and f) one or more sweeteners; whereby component a)is packaged in a first compartment and components b), c) e) and f) arepackaged in a second compartment.
 19. A kit as claimed in claim 18wherein the first component comprises mango flavouring, sucralose andcitric acid; and the second component comprises aspartame and aflavouring selected from lemon, kiwi, strawberry, grapefruit, orange,fruit punch and mango.
 20. A kit as claimed in claim 18 wherein thefirst and second components are dry powders.
 21. A kit comprising: afirst colon cleansing agent, the first colon cleansing agent solutioncomprising: (i) 70 to 250 g per litre PEG having an average molecularweight of 2500 to 4500 Da. (ii) 2.0 to 20 g per litre of one or morealkali metal sulphates, alkaline earth metal sulphates or a mixturethereof (iii) optionally one or more electrolytes; (iv) optionally oneor more flavouring agents; and (v) optionally one or more sweeteners,and a second colon cleansing agent, the second colon agent solutionbeing a solution in water of: a) 300 to 800 mmol per litre ascorbateanion provided by a mixture of (i) ascorbic acid and (ii) one or moresalts of ascorbic acid the components (i) and (ii) being present in amolar ratio of from 1:4.5 to 1:7.0; and b) 10 to 200 g per litrepolyethylene glycol.
 22. A kit as claimed in claim 21 wherein the firstcolon cleansing solution comprises: (i) 175 to 220 g per litre PEGhaving an average molecular weight of 2500 to 4500 Da. (ii) 15 to 20 gper litre of one or more alkali metal sulphates, alkaline earth metalsulphates or a mixture thereof (iii) 3.0 to 5.0 g per litre sodiumchloride, and 1.5 to 2.5 g per litre potassium chloride; (iv) optionallyone or more flavouring agents; and (v) optionally one or moresweeteners.
 23. A kit as claimed in claim 21 wherein the second coloncleansing solution comprises: a) (i) 12 to 20 g per litre ascorbic acidand (ii) 80 to 120 g per litre sodium ascorbate the components (i) and(ii) being present in a weight ratio of from 1:5063 to 1:7.875; b) 60 to100 g per litre PEG having an average molecular weight of 3000 to 4000Da; c) 3 to 8 g per litre sodium chloride and 1 to 7 g per litrepotassium chloride; e) one or more flavouring agents; and f) one or moresweeteners.
 24. A kit as claimed in claim 21 comprising: a first coloncleansing agent, the first colon cleansing agent solution comprising:(i) 200 g per litre PEG having an average molecular weight of 3350 Da.(ii) 18 g per litre sodium sulphate (iii) 4.0 g per litre sodiumchloride, and 2.0 g per litre potassium chloride (iv) one or moreflavouring agents; and (v) one or more sweeteners, and a second coloncleansing agent, the second colon agent solution being a solutionconsisting essentially of: a) 15.08 g per litre ascorbic acid and 96.22g per litre sodium ascorbate b) 80 g per litre PEG having an averagemolecular weight of 3000 to 4000 Da; c) 6.4 g per litre sodium chlorideand 2.4 g per litre potassium chloride; e) one or more flavouringagents; and f) one or more sweeteners.